116 results on '"Avitabile E"'
Search Results
2. Torino Metro Line 1 extension: Working solutions
- Author
-
Damiani, A., primary, Mancinelli, L., additional, Crova, R., additional, and Avitabile, E., additional
- Published
- 2019
- Full Text
- View/download PDF
3. CD68 + Cells of Monocyte/Macrophage Lineage in the Environment of AIDS-Associated and Classic-Sporadic Kaposi Sarcoma are Singly or Doubly Infected with Human Herpesviruses 7 and 6B
- Author
-
Kempf, W., Adams, V., Wey, N., Moos, R., Schmid, M., Avitabile, E., and Campadelli-Fiume, G.
- Published
- 1997
4. Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis
- Author
-
Pose, Elisa, Solà, Elsa, Lozano, Juan J., Juanola, Adrià, Sidorova, Julia, Zaccherini, Giacomo, Wit, Koos, Uschner, Frank, Tonon, Marta, Kazankov, Konstantin, Jiménez, Cesar, Campion, Daniela, Napoleone, Laura, Ma, Ann T., Carol, Marta, Morales‐Ruiz, Manuel, Alessandria, Carlo, Beuers, Ulrich, Caraceni, Paolo, Francoz, Claire, Durand, François, Mookerjee, Rajeshwar P., Trebicka, Jonel, Vargas, Victor, Piano, Salvatore, Watson, Hugh, Abraldes, Juan G., Kamath, Patrick S., Davis, Mark M., Ginès, Pere, Schulz, M., Ferstl, P., Giovo, I., Roux, O., Simon‐Talero, M., Pérez‐Guasch, M., Rubio, A.B., Cervera, M., Martínez, S., Fabrellas, N., Pich, J., Vives, A., Avitabile, E., Graupera, I., Solé, C., Bassegoda, O., Gratacós‐Ginès, J., Joyera, M., Palacio, E., Aban, M., Lanzillotti, T., Nicolao, G., Chiappa, M.T., Esnault, V., Andrade, R., Pavesi, M., Korenjak, M., Farrés, J., Serra‐Burriel, M., Angeli, P., Pose E., Sola E., Lozano J.J., Juanola A., Sidorova J., Zaccherini G., de Wit K., Uschner F., Tonon M., Kazankov K., Jimenez C., Campion D., Napoleone L., Ma A.T., Carol M., Morales-Ruiz M., Alessandria C., Beuers U., Caraceni P., Francoz C., Durand F., Mookerjee R.P., Trebicka J., Vargas V., Piano S., Watson H., Abraldes J.G., Kamath P.S., Davis M.M., Gines P., Schulz M., Ferstl P., Giovo I., Roux O., Simon-Talero M., Perez-Guasch M., Rubio A.B., Cervera M., Martinez S., Fabrellas N., Pich J., Vives A., Avitabile E., Graupera I., Sole C., Bassegoda O., Gratacos-Gines J., Joyera M., Palacio E., Aban M., Lanzillotti T., Nicolao G., Chiappa M.T., Esnault V., Andrade R., Pavesi M., Korenjak M., Farres J., Serra-Burriel M., Angeli P., Gastroenterology and Hepatology, Graduate School, Tytgat Institute for Liver and Intestinal Research, and Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
Liver Cirrhosis ,0303 health sciences ,Simvastatin ,Hepatology ,Kynurenine/therapeutic use ,Tryptophan ,Acute-On-Chronic Liver Failure ,Tryptophan/therapeutic use ,Rifaximin ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,simvastatin and rifaximin ,Simvastatin/therapeutic use ,Carnitine ,Humans ,Metabolomics ,030211 gastroenterology & hepatology ,Carnitine/therapeutic use ,Rifaximin/therapeutic use ,Kynurenine ,030304 developmental biology ,Liver Cirrhosis/drug therapy - Abstract
Patients with decompensated cirrhosis, particularly those with acute-on-chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE-SAFETY randomized, double-blind, placebo-controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography-tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan-kynurenine and carnitine beta-oxidation pathways. An ACLF-specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan-kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.
- Published
- 2021
5. Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis
- Author
-
Pose, Elisa, primary, Solà, Elsa, additional, Lozano, Juan J., additional, Juanola, Adrià, additional, Sidorova, Julia, additional, Zaccherini, Giacomo, additional, de Wit, Koos, additional, Uschner, Frank, additional, Tonon, Marta, additional, Kazankov, Konstantin, additional, Jiménez, Cesar, additional, Campion, Daniela, additional, Napoleone, Laura, additional, Ma, Ann T., additional, Carol, Marta, additional, Morales-Ruiz, Manuel, additional, Alessandria, Carlo, additional, Beuers, Ulrich, additional, Caraceni, Paolo, additional, Francoz, Claire, additional, Durand, François, additional, Mookerjee, Rajeshwar P., additional, Trebicka, Jonel, additional, Vargas, Victor, additional, Piano, Salvatore, additional, Watson, Hugh, additional, Abraldes, Juan G., additional, Kamath, Patrick S., additional, Davis, Mark M., additional, Ginès, Pere, additional, Schulz, M., additional, Ferstl, P., additional, Giovo, I., additional, Roux, O., additional, Simon-Talero, M., additional, Pérez-Guasch, M., additional, Rubio, A. B., additional, Cervera, M., additional, Martínez, S., additional, Fabrellas, N., additional, Pich, J., additional, Vives, A., additional, Avitabile, E., additional, Graupera, I., additional, Solé, C., additional, Bassegoda, O., additional, Gratacós-Ginès, J., additional, Joyera, M., additional, Palacio, E., additional, Aban, M., additional, Lanzillotti, T., additional, Nicolao, G., additional, Chiappa, M. T., additional, Esnault, V., additional, Andrade, R., additional, Pavesi, M., additional, Korenjak, M., additional, Farrés, J., additional, Serra-Burriel, M., additional, and Angeli, P., additional
- Published
- 2022
- Full Text
- View/download PDF
6. Nanocytometer for smart analysis of peripheral blood and acute myeloid leukemia: a pilot study
- Author
-
(0000-0002-2593-3021) Schütt, J., Sandoval Bojorquez, D. I., Avitabile, E., Oliveros Mata, E. S., Milyukov, G., Colditz, J., Delogu, L. G., Rauner, M., (0000-0001-5099-2448) Feldmann, A., Koristka, S., Middeke, J. M., Sockel, K., (0000-0003-3893-9630) Faßbender, J., (0000-0002-8029-5755) Bachmann, M., Bornhäuser, M., Cuniberti, G., (0000-0003-1010-2791) Baraban, L., (0000-0002-2593-3021) Schütt, J., Sandoval Bojorquez, D. I., Avitabile, E., Oliveros Mata, E. S., Milyukov, G., Colditz, J., Delogu, L. G., Rauner, M., (0000-0001-5099-2448) Feldmann, A., Koristka, S., Middeke, J. M., Sockel, K., (0000-0003-3893-9630) Faßbender, J., (0000-0002-8029-5755) Bachmann, M., Bornhäuser, M., Cuniberti, G., and (0000-0003-1010-2791) Baraban, L.
- Abstract
We realize an ultracompact nanocytometer for real-time impedimetric detection and classification of subpopulations ofliving cells. Nanoscopic nanowires in a microfluidic channel act asnanocapacitors and measure in real time the change of theamplitude and phase of the output voltage and, thus, the electricalproperties of living cells. We perform the cell classification in thehuman peripheral blood (PBMC) and demonstrate for thefirsttime the possibility to discriminate monocytes andsubpopulationsof lymphocytes in a label-free format. Further, we demonstrate thatthe PBMC of acute myeloid leukemia and healthy samples grantthe label free identification of the disease. Using the algorithmbased on machine learning, we generatedspecific data patternstodiscriminate healthy donors and leukemia patients. Such a solutionhas the potential to improve the traditional diagnostics approaches with respect to the overall cost and time effort, in a label-freeformat, and restrictions of the complex data analysis.
- Published
- 2020
7. Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium
- Author
-
Solà, Elsa, primary, Pose, Elisa, additional, Campion, Daniela, additional, Piano, Salvatore, additional, Roux, Olivier, additional, Simon-Talero, Macarena, additional, Uschner, Frank, additional, de Wit, Koos, additional, Zaccherini, Giacomo, additional, Alessandria, Carlo, additional, Beuers, Ulrich, additional, Caraceni, Paolo, additional, Francoz, Claire, additional, Mookerjee, Rajeshwar P., additional, Trebicka, Jonel, additional, Vargas, Victor, additional, Serra, Miquel, additional, Torres, Ferran, additional, Montagnese, Sara, additional, Krag, Aleksander, additional, Hernaez, Ruben, additional, Korenjak, Marko, additional, Watson, Hugh, additional, Abraldes, Juan G., additional, Kamath, Patrick S., additional, Ginès, Pere, additional, Durand, F., additional, Bernardi, M., additional, Solé, C., additional, Pich, J., additional, Graupera, I., additional, Napoleone, L., additional, Jiménez, C., additional, Juanola, A., additional, Avitabile, E., additional, Ma, A., additional, Fabrellas, N., additional, Carol, M., additional, Palacio, E., additional, Aban, M., additional, Lanzillotti, T., additional, Nicolao, G., additional, Chiappa, M.T., additional, Esnault, V., additional, Forner, A., additional, Graf-Dirmeier, S., additional, Helder, J., additional, Lopez, M., additional, Cervera, M., additional, and Pérez-Guasch, M., additional
- Published
- 2021
- Full Text
- View/download PDF
8. CD68+ cells of monocyte/macrophage lineage in the environment of AIDS-associated and classic-sporadic Kaposi sarcoma are singly or doubly infected with human herpesviruses 7 and 6
- Author
-
Kempf, W., Adams, V., Wey, N., Moos, R., Schmid, M., Avitabile, E., and Campadelli-Fiume, G.
- Subjects
Cell lines -- Physiological aspects ,Kaposi's sarcoma -- Research ,AIDS (Disease) -- Research ,Herpesviruses -- Research ,Virus diseases -- Research ,Science and technology - Abstract
Earlier studies have shown that Kaposi sarcomas contain cells infected with human herpesvirus (HHV) 6B, and in current studies we report that both AIDS-associated and classic-sporadic Kaposi sarcoma contain HHV-7 genome sequences detectable by PCR. To determine the distribution of HHV-7-infected cells relative to those infected with HHV-6, sections from paraffin-embedded tissues were allowed to react with antibodies to HHV-7 virion tegument phosphoprotein pp85 and to HHV-6B protein p101. The antibodies are specific for HHV-7 and HHV-6B, respectively, and they retained reactivity for antigens contained in formalin-fixed, paraffin-embedded tissue samples. We report that (i) HHV-7 pp85 was present in 9 of 32 AIDS-associated Kaposi sarcomas, and in 1 of 7 classical-sporadic HIV-negative Kaposi sarcomas; (ii) HHV-7 pp85 was detected primarily in cells bearing the CD68 marker characteristic of the monocyte/macrophage lineage present in or surrounding the Kaposi sarcoma lesions; and (iii) in a number of Kaposi sarcoma specimens, tumor-associated [CD68.sup.+] monocytes/macrophages expressed simultaneously antigens from both HHV-7 and HHV-6B, and therefore appeared to be doubly infected with the two viruses. [CD68.sup.+] monocytes/macrophages infected with HHV-7 were readily detectable in Kaposi sarcoma, but virtually absent from other normal or pathological tissues that harbor macrophages. Because all of the available data indicate that HHV-7 infects [CD4.sup.+] T lymphocytes, these results suggest that the environment of the Kaposi sarcoma (i) attracts circulating peripheral lymphocytes and monocytes, triggers the replication of latent viruses, and thereby increases the local concentration of viruses, (ii) renders [CD68.sup.+] monocytes/macrophages susceptible to infection with HHV-7, and (iii) the combination of both events enables double infections of cells with both HHV-6B and HHV-7.
- Published
- 1997
9. Cognitive deterioration in bilateral asymptomatic carotid stenosis
- Author
-
Buratti L, Balucani C, Viticchi G, Falsetti L, Altamura C, Avitabile E, Provinciali L, Vernieri F, Silvestrini M, Antonio Federico, and Buratti L, Balucani C, Viticchi G, Falsetti L, Altamura C, Avitabile E, Provinciali L, Vernieri F, Silvestrini M
- Subjects
cognitive deterioration ,carotid atherosclerosi - Published
- 2014
10. Sex-associated differences in the modulation of vascular risk in patients with asymptomatic carotid stenosis
- Author
-
Buratti L, Balestrini S, Avitabile E, Altamura C, Vernieri F, Viticchi G, Falsetti L, Provinciali L, Silvestrini M, Antonio Federico, and Buratti L, Balestrini S, Avitabile E, Altamura C, Vernieri F, Viticchi G, Falsetti L, Provinciali L, Silvestrini M
- Subjects
gender difference ,carotid atherosclerosis - Published
- 2014
11. La glicoproteina D di HSV-1 blocca l'apoptosi mediata da Fas in cellule U937
- Author
-
Sciortino, Maria Teresa, Perri, D, Medici, Ma, Avitabile, E, Valveri, V, Spagnolo, A, D'Ascola, Angela, and Mastino, Antonio
- Published
- 2001
12. HSV-1 inibisce l'apoptosi mediata da Fas in cellule U937 mediante attivazione di NF-kB
- Author
-
Perri, D, Sciortino, Maria Teresa, Medici, Maria Antonietta, Avitabile, E, Valveri, V, Ciotti, M, Matteucci, C, Amici, C, DE SMAELE, E, and Mastino, Antonio
- Published
- 2001
13. Retinoids and Cancer: Antitumoral Effects of ATRA, 9-cis RA and the New Retinoid IIF on the HL-60 Leukemic Cell Line
- Author
-
Orlandi, M., primary, Mantovani, B., additional, Ammar, K., additional, Avitabile, E., additional, Dal Monte, P., additional, and Bartolini, G., additional
- Published
- 2003
- Full Text
- View/download PDF
14. CD68+cells of monocyte/macrophage lineage in the environment of AIDS-associated and classic-sporadic Kaposi sarcoma are singly or doubly infected with human herpesviruses 7 and 6B
- Author
-
Kempf, W., primary, Adams, V., additional, Wey, N., additional, Moos, R., additional, Schmid, M., additional, Avitabile, E., additional, and Campadelli-Fiume, G., additional
- Published
- 1997
- Full Text
- View/download PDF
15. Identification of an 85 kDa phosphoprotein as an immunodominant protein specific for human herpesvirus 7-infected cells
- Author
-
Foa-Tomasi, L., primary, Fiorilli, M. P., additional, Avitabile, E., additional, and Campadelli-Fiume, G., additional
- Published
- 1996
- Full Text
- View/download PDF
16. Redistribution of microtubules and Golgi apparatus in herpes simplex virus-infected cells and their role in viral exocytosis
- Author
-
Avitabile, E, primary, Di Gaeta, S, additional, Torrisi, M R, additional, Ward, P L, additional, Roizman, B, additional, and Campadelli-Fiume, G, additional
- Published
- 1995
- Full Text
- View/download PDF
17. The herpes simplex virus UL20 protein compensates for the differential disruption of exocytosis of virions and viral membrane glycoproteins associated with fragmentation of the Golgi apparatus
- Author
-
Avitabile, E, primary, Ward, P L, additional, Di Lazzaro, C, additional, Torrisi, M R, additional, Roizman, B, additional, and Campadelli-Fiume, G, additional
- Published
- 1994
- Full Text
- View/download PDF
18. Localization and putative function of the UL20 membrane protein in cells infected with herpes simplex virus 1
- Author
-
Ward, P L, primary, Campadelli-Fiume, G, additional, Avitabile, E, additional, and Roizman, B, additional
- Published
- 1994
- Full Text
- View/download PDF
19. Polyvalent and monoclonal antibodies identify major immunogenic proteins specific for human herpesvirus 7-infected cells and have weak cross-reactivity with human herpesvirus 6
- Author
-
Foa-Tomasi, L., primary, Avitabile, E., additional, Ke, L., additional, and Campadelli-Fiume, G., additional
- Published
- 1994
- Full Text
- View/download PDF
20. Glycoprotein D of herpes simplex virus encodes a domain which precludes penetration of cells expressing the glycoprotein by superinfecting herpes simplex virus
- Author
-
Campadelli-Fiume, G, primary, Qi, S, additional, Avitabile, E, additional, Foà-Tomasi, L, additional, Brandimarti, R, additional, and Roizman, B, additional
- Published
- 1990
- Full Text
- View/download PDF
21. Nectin2alpha (PRR2alpha or HveB) and nectin2delta are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D.
- Author
-
Lopez, M, Cocchi, F, Menotti, L, Avitabile, E, Dubreuil, P, and Campadelli-Fiume, G
- Abstract
The receptors for entry of herpes simplex viruses 1 and 2 (HSV-1 and -2), widely expressed in human cell lines, are members of a subset of the immunoglobulin superfamily exemplified by herpesvirus entry mediator C (HveC) and the herpesvirus immunoglobulin-like receptor (HIgR). This report focuses on two members of this subset, herpesvirus entry mediator B (HveB), recently designated nectin2/PRR2alpha, and its splice variant isoform, nectin2/PRR2delta. Nectin2alpha and -delta share the ectodomain but differ in the transmembrane and cytoplasmic regions. HveB was reported to enable entry of HSV-1 carrying mutations in glycoprotein D (gD) and of HSV-2, but not of wild-type (wt) HSV-1. We report that (i) both nectin2alpha and -delta served as receptors for the entry of HSV-1 mutant viruses HSV-1(U10) and -(U21) and AP7(r) that carry the Leu25Pro substitution in gD but not for HSV-1 mutants U30 and R5000 that carry the Ser140 or Ala185 substitution in gD. All of these mutants were able to overcome the block to entry mediated by expression of wt gD. (ii) Infection of cells expressing nectin2alpha or -delta required exposure to multiplicities of infection about 100-fold higher than those required to infect cells expressing HveC or HIgR. (iii) gD from HSV-1(U21) bound in vitro soluble forms of nectin2. The association was weaker than that to the soluble form of HveC/HIgR. Binding of wt HSV-1 gD to soluble nectin2 was not detectable. (iv) A major region of nectin2 functional in virus entry mapped to the V domain, located at the N terminus.
- Published
- 2000
22. SARS-CoV-2/COVID-19 testing: The tower of babel
- Author
-
Reno, Chiara, Lenzi, Jacopo, Golinelli, Davide, Gori, Davide, Signorelli, Carlo, Kraemer, John, Stoto, Michael A., Avitabile, Elisa, Landini, Maria Paola, Lazzarotto, Tiziana, Re, Maria Carla, Rucci, Paola, Taliani, Gloria, Trerè, Davide, Vocale, Caterina, Fantini, Maria Pia, Reno, C., Lenzi, J., Golinelli, D., Gori, D., Signorelli, C., Kraemer, J., Stoto, M. A., Avitabile, E., Landini, M. P., Lazzarotto, T., Carla Re, M., Rucci, P., Taliani, G., Trerè, D., Vocale, C., Fantini, M. P., Reno C., Lenzi J., Golinelli D., Gori D., Signorelli C., Kraemer J., Stoto M.A., Avitabile E., Landini M.P., Lazzarotto T., Re M.C., Rucci P., Taliani G., Trere' D., Vocale C., and Fantini M.P.
- Subjects
Pandemic ,SARS-CoV-2 ,Reproducibility of Results ,COVID-19 ,Original Investigations/Commentaries ,Molecular diagnostic technique ,Pooling test ,COVID-19 Testing ,ROC Curve ,Molecular diagnostic techniques ,Predictive value of tests ,Public health surveillance ,Rapid antigen test ,Screening ,Humans ,Predictive value of test - Abstract
Summary. Background and aim: Testing represents one of the main pillars of public health response to SARS-CoV-2/COVID-19 pandemic. This paper shows how accuracy and utility of testing programs depend not just on the type of tests, but on the context as well. Methods: We describe the testing methods that have been developed and the possible testing strategies; then, we focus on two possible methods of population-wide testing, i.e., pooled testing and testing with rapid antigen tests. We show the accuracy of split-pooling method and how, in different pre-test probability scenarios, the positive and negative predictive values vary using rapid antigen tests. Results: Split-pooling, followed by retesting of negative results, shows a higher sensitivity than individual testing and requires fewer tests. In case of low pre-test probability, a negative result with antigen test could allow to rule out the infection, while, in case of a positive result, a confirmatory molecular test would be necessary. Conclusions: Test performance alone is not enough to properly choose which test to use; goals and context of the testing program are essential. We advocate the use of pooled strategies when planning population-wide screening, and the weekly use of rapid tests for close periodic monitoring in low-prevalence populations. (www.actabiomedica.it).
- Published
- 2020
23. Selection of a monoclonal antibody specific for variant B human herpesvirus 6-infected mononuclear cells
- Author
-
Foa-Tomasi, L., Avitabile, E., and Campadelli-Fiume, G.
- Published
- 1995
- Full Text
- View/download PDF
24. Impact of the surface functionalization on nanodiamond biocompatibility: a comprehensive view on human blood immune cells
- Author
-
Laura Fusco, Elisabetta Avitabile, Tatiana Da Ros, Valentina Armuzza, Marco Orecchioni, Davide Bedognetti, Akcan Istif, Lucia Gemma Delogu, Fusco, L., Avitabile, E., Armuzza, V., Orecchioni, M., Istif, A., Bedognetti, D., Da Ros, T., and Delogu, L. G.
- Subjects
Biocompatibility ,Chemistry ,medicine.medical_treatment ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Peripheral blood mononuclear cell ,3. Good health ,0104 chemical sciences ,Cell biology ,Proinflammatory cytokine ,Cytokine ,Immune system ,nanodiamonds ,Gene expression ,medicine ,General Materials Science ,Cytokine secretion ,Viability assay ,0210 nano-technology - Abstract
Nanodiamonds (NDs) represent a class of carbon nanostructures widely investigated as promising biomedical nanotools. The possible immune system reactions indicate success or failure for any nanosystem bioapplication. Moreover the assessment of the role of nanomaterial functionalization on the immune system response needs to be fully elucidated. We aimed to dissect the immunologic impact of two NDs differing for their functionalization, carboxylic acid modified NDs (NDs-COOH) and amino-functionalized NDs (NDs-NH2), presenting a glycolic chain as spacer. We used human peripheral blood mononuclear cells (PBMCs) as model for potential biomedical scenario of NDs interaction with the human body. The ND immunologic effects were depicted toward the complex mix of PBMCs. The results showed that both functionalizations possess high hemocompatibility but NDs-COOH induced a cell viability reduction, affecting monocytes. The ND impact was depicted through immune activation markers, immune-response gene expression and cytokine secretion analysis. Immune markers confirmed the impact on monocytes, more evident for NDs-COOH. Both NDs affected the immune response, however NDs-COOH showed more prominent responses, evoking pronounced regulation of immune-modulatory transcripts. The cytokine analysis confirmed gene expression data for proinflammatory cytokines related to the innate response. Our findings reveal that NDs decoration with an amino-terminating chain enhances their immunologic compatibility.
- Published
- 2020
25. Specificity, Safety, Efficacy of EGFRvIII-Retargeted Oncolytic HSV for Xenotransplanted Human Glioblastoma
- Author
-
Gabriella Campadelli-Fiume, Noemi Piga, Irene Appolloni, Francesca Piaggio, Elisa Avitabile, Paolo Malatesta, Francesco Alessandrini, Davide Ceresa, Daniela Marubbi, Laura Menotti, Appolloni I., Alessandrini F., Menotti L., Avitabile E., Marubbi D., Piga N., Ceresa D., Piaggio F., Campadelli-Fiume G., and Malatesta P.
- Subjects
HSL and HSV ,Herpesvirus 1, Human ,Mice, SCID ,medicine.disease_cause ,Virus Replication ,Mice ,0302 clinical medicine ,Chlorocebus aethiops ,Medicine ,Epidermal growth factor receptor ,Oncolytic Virotherapy ,0303 health sciences ,Mutation ,biology ,glioblastoma stem cells ,EGFRvIII ,Glioblastoma initiating cells ,Glioblastoma stem cells ,Oncolytic HSV ,Oncolytic virotherapy ,QR1-502 ,3. Good health ,ErbB Receptors ,Oncolytic Viruses ,Infectious Diseases ,030220 oncology & carcinogenesis ,Median survival ,Genetic Vectors ,Transplantation, Heterologous ,Brain tumor ,Microbiology ,Article ,03 medical and health sciences ,Virology ,Cell Line, Tumor ,glioblastoma initiating cells ,Animals ,Humans ,Glioblastoma stem cell ,Vero Cells ,030304 developmental biology ,Glioblastoma initiating cell ,business.industry ,oncolytic HSV ,medicine.disease ,Oncolytic virus ,Cancer research ,biology.protein ,business ,Glioblastoma ,Ex vivo - Abstract
Glioblastoma is a lethal primary brain tumor lacking effective therapy. The secluded onset site, combined with the infiltrative properties of this tumor, require novel targeted therapies. In this scenario, the use of oncolytic viruses retargeted to glioblastoma cells and able to spread across the tumor cells represent an intriguing treatment strategy. Here, we tested the specificity, safety and efficacy of R-613, the first oncolytic HSV fully retargeted to EGFRvIII, a variant of the epidermal growth factor receptor carrying a mutation typically found in glioblastoma. An early treatment with R-613 on orthotopically transplanted EGFRvIII-expressing human glioblastoma significantly increased the median survival time of mice. In this setting, the growth of human glioblastoma xenotransplants was monitored by a secreted luciferase reporter and showed that R-613 is able to substantially delay the development of the tumor masses. When administered as late treatment to a well-established glioblastomas, R-613 appeared to be less effective. Notably the uninfected tumor cells derived from the explanted tumor masses were still susceptible to R-613 infection ex vivo, thus suggesting that multiple treatments could enhance R-613 therapeutic efficacy, making R-613 a promising oncolytic HSV candidate for glioblastoma treatment.
- Published
- 2021
26. Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy
- Author
-
Laura Menotti, Elisa Avitabile, Menotti L., and Avitabile E.
- Subjects
Oncology ,medicine.medical_specialty ,Poor prognosis ,Combination therapy ,Herpesvirus 1, Human ,Review ,Immune checkpoint inhibitor ,medicine.disease_cause ,Catalysis ,tropism retargeting ,immune checkpoint inhibitors ,Inorganic Chemistry ,lcsh:Chemistry ,Internal medicine ,medicine ,Humans ,Simplexvirus ,Herpes simplex viru ,Physical and Theoretical Chemistry ,Virotherapy ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,oncolytic virus ,Oncolytic Virotherapy ,genetic engineering ,business.industry ,Organic Chemistry ,Oncolytic viru ,Cancer ,Oncolytic immunoviroterapy ,Multimodal therapy ,General Medicine ,medicine.disease ,herpes simplex virus ,Combined Modality Therapy ,Computer Science Applications ,Oncolytic virus ,Oncolytic Viruses ,Herpes simplex virus ,Innovative Therapies ,lcsh:Biology (General) ,lcsh:QD1-999 ,virus arming ,virotherapy ,business - Abstract
Oncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to self-exhaust upon tumor clearance. Oncolytic virotherapy strategies based on the herpes simplex virus are reaching their thirties, and a wide variety of approaches has been envisioned and tested in many different models, and on a range of tumor targets. This huge effort has culminated in the primacy of an oncolytic HSV (oHSV) being the first oncolytic virus to be approved by the FDA and EMA for clinical use, for the treatment of advanced melanoma. The path has just been opened; many more cancer types with poor prognosis await effective and innovative therapies, and oHSVs could provide a promising solution, especially as combination therapies and immunovirotherapies. In this review, we analyze the most recent advances in this field, and try to envision the future ahead of oHSVs.
- Published
- 2020
27. Coexpression of UL20p and gK Inhibits Cell-Cell Fusion Mediated by Herpes Simplex Virus Glycoproteins gD, gH-gL, and Wild-Type gB or an Endocytosis-Defective gB Mutant and Downmodulates Their Cell Surface Expression
- Author
-
Gabriella Campadelli-Fiume, Elisa Avitabile, Giulia Lombardi, Miriam Capri, Tatiana Gianni, AVITABILE E., LOMBARDI G., GIANNI T., CAPRI M., and CAMPADELLI-FIUME G.
- Subjects
DOWN-REGULATION ,Syncytium ,Cell fusion ,HERPES SIMPLEX ,MEMBRANE FUSION ,ENDOCYTOSIS ,Endoplasmic reticulum ,Immunology ,Lipid bilayer fusion ,Biology ,Endocytosis ,Microbiology ,Herpesvirus glycoprotein B ,Molecular biology ,Virus-Cell Interactions ,Cell Line ,VIRAL GLYCOPROTEINS ,Viral Proteins ,Viral Envelope Proteins ,Cytoplasm ,Cell culture ,Virology ,Insect Science ,Animals - Abstract
Syncytium formation in cells that express herpes simplex virus glycoprotein B (gB), gD, gH, and gL is blocked by gK (E. Avitabile, G. Lombardi, and G. Campadelli-Fiume, J. Virol. 77: 6836-6844, 2003). Here, we report the results of two series of experiments. First, UL20 protein (UL20p) expression weakly inhibited cell-cell fusion. Coexpression of UL20p and gK drastically reduced fusion in a cell-line-dependent manner, with the highest inhibition in BHK cells. Singly expressed UL20p and gK localized at the endoplasmic reticulum and nuclear membranes. When they were coexpressed, both proteins relocalized to the Golgi apparatus. Remarkably, in cells that coexpressed UL20p and gK, the antifusion activity correlated with a downmodulation of gD, gB, gH, and gL cell surface expression. Second, gB Δ867 has a partial deletion in the cytoplasmic tail that removed endocytosis motifs. Whereas wild-type (wt) gB was internalized in vesicles lined with the endosomal marker Rab5, gB Δ867 was not internalized, exhibited enhanced cell surface expression, and was more efficient in mediating cell-cell fusion than wt gB. The antifusion activity of UL20p and gK was also exerted when gB Δ867 replaced wt gB in the cell fusion assay. These studies show that the gB C tail carries a functional endocytosis motif(s) and that the removal of the motif correlated with increased gB surface expression and increased fusion activity. We conclude that cell-cell fusion in wt-virus-infected cells is negatively controlled by at least two mechanisms. The novel mechanism described here involves the concerted action of UL20p and gK and correlates with a moderate but consistent reduction in the cell surface expression of the fusion glycoproteins. This mechanism is independent of the one exerted through endocytosis-mediated downmodulation of gB from the plasma membrane.
- Published
- 2004
28. The Domains of Glycoprotein D Required To Block Apoptosis Induced by Herpes Simplex Virus 1 Are Largely Distinct from Those Involved in Cell-Cell Fusion and Binding to Nectin1
- Author
-
Elisa Avitabile, Bernard Roizman, Gabriella Campadelli-Fiume, Guoying Zhou, Zhou G., Avitabile E., Campadelli-Fiume G., and Roizman B.
- Subjects
Glycosylation ,Nectins ,Immunology ,Mutant ,Glycoprotein D (gD), nectin1, herpes simplex virus (HSV), cell-cell fusion, apoptosis, gD-/+ virus ,Apoptosis ,Herpesvirus 1, Human ,Spodoptera ,Biology ,medicine.disease_cause ,Microbiology ,Cell Line ,Cell Fusion ,chemistry.chemical_compound ,Viral Envelope Proteins ,Cricetinae ,Virology ,medicine ,Animals ,Humans ,Receptor ,chemistry.chemical_classification ,Mutation ,Cell fusion ,Herpesvirus glycoprotein B ,Molecular biology ,Virus-Cell Interactions ,chemistry ,Ectodomain ,Insect Science ,Receptors, Virus ,Glycoprotein ,Cell Adhesion Molecules - Abstract
Glycoprotein D (gD) interacts with two alternative protein receptors, nectin1 and HveA, to mediate herpes simplex virus (HSV) entry into cells. Fusion of the envelope with the plasma membrane requires, in addition to gD, glycoproteins gB, gH, and gL. Coexpression of the four glycoproteins (gD, gB, gH, and gL) promotes cell-cell fusion. gD delivered in trans is also capable of blocking the apoptosis induced by gD deletion viruses grown either in noncomplementing cells (gD −/− ) or in complementing cells (gD −/+ ). While ectopic expression of cation-independent mannose-6 phosphate receptor blocks apoptosis induced by both stocks, other requirements differ. Thus, apoptosis induced by gD −/− virus is blocked by full-length gD (or two gD fragments reconstituting a full-length molecule), whereas ectopic expression of the gD ectodomain is sufficient to block apoptosis induced by gD −/+ virus. In this report we took advantage of a set of gD insertion-deletion mutants to map the domains of gD required to block apoptosis by gD −/− and gD −/+ viruses and those involved in cell-cell fusion. The mutations that resulted in failure to block apoptosis were the same for gD −/− and gD −/+ viruses and were located in three sites, one within the immunoglobulin-type core region (residues 125, 126, and 151), one in the upstream connector region (residues 34 and 43), and one in the C-terminal portion of the ectodomain (residue 277). A mutant that carried amino acid substitutions at the three glycosylation sites failed to block apoptosis but behaved like wild-type gD in all other assays. The mutations that inhibited polykaryocyte formation were located in the upstream connector region (residues 34 and 43), at the α1 helix (residue 77), in the immunoglobulin core and downstream regions (residue 151 and 187), and at the α3 helix (residues 243 and 246). Binding of soluble nectin1-Fc to cells expressing the mutant gDs was generally affected by the same mutations that affected fusion, with one notable exception (Δ277-310), which affected fusion without hampering nectin1 binding. This deletion likely identifies a region of gD involved in fusion activity at a post-nectin1-binding step. We conclude that whereas mutations that affected all functions (e.g., upstream connector region and residue 151) may be detrimental to overall gD structure, the mutations that affect specific activities identify domains of gD involved in the interactions with entry receptors and fusogenic glycoproteins and with cellular proteins required to block apoptosis. The evidence that glycosylation of gD is required for blocking apoptosis supports the conclusion that the interacting protein is the mannose-6 phosphate receptor.
- Published
- 2003
29. The murine homolog of human Nectin1δ serves as a species nonspecific mediator for entry of human and animal αherpesviruses in a pathway independent of a detectable binding to gD
- Author
-
Francesca Cocchi, Eric Lecocq, Elisa Avitabile, Alessandra Stefan, José Adélaïde, Laura Menotti, Gabriella Campadelli-Fiume, Patrice Dubreuil, Marc Lopez, Menotti L., Lopez M., Avitabile E., Stefan A., Cocchi F., Adelaide J., Lecocq E., Dubreuil P., and Campadelli-Fiume G.
- Subjects
Virus genetics ,Simplexvirus ,Herpesvirus entry mediator ,DNA, Complementary ,food.ingredient ,Swine ,viruses ,Molecular Sequence Data ,Nectins ,3T3 Cells Alphaherpesvirinae/*physiology Amino Acid Sequence Animals CHO Cells Cattle Cell Adhesion Molecules/chemistry/genetics/*physiology Cloning, Molecular Conserved Sequence DNA, Complementary Hamsters Human Immunoglobulin D/*metabolism Mice Molecular Sequence Data Receptors, Virus/chemistry/genetics/*physiology Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Sequence Homology, Amino Acid Simplexvirus/*physiology Support, Non-U.S. Gov't Swine ,CHO Cells ,Alphaherpesvirinae ,Transfection ,medicine.disease_cause ,Virus ,Mice ,food ,Cricetinae ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Cloning, Molecular ,Conserved Sequence ,Infectivity ,Multidisciplinary ,Sequence Homology, Amino Acid ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Membrane Proteins ,3T3 Cells ,Immunoglobulin D ,Biological Sciences ,biology.organism_classification ,Herpesvirus glycoprotein B ,Virology ,Molecular biology ,Bovine herpesvirus 1 ,Herpes simplex virus ,Receptors, Virus ,Cattle ,Cell Adhesion Molecules ,Sequence Alignment - Abstract
The full-length cDNA of the murine homolog of human nectin1delta (mNectin1delta), also known as human poliovirus receptor related 1 (PRR1) or herpesvirus entry mediator C, was cloned and showed a90% identity with its human counterpart. mNectin1delta is expressed in some murine cell lines, exemplified by NIH 3T3 and L cells, and in murine tissues. It mediates entry of an extended range of herpes simplex virus (HSV) strains, porcine pseudorabies virus (PrV), and bovine herpesvirus 1. A soluble form of the mediator blocked infectivity in mNectin1delta and human nectin1delta (hNectin1delta)-expressing cells, suggesting a physical interaction of the mediator with virions. The higher concentrations of soluble mNectin1 required to block infectivity relative to soluble hNectin1 suggest that the target of the two molecules is not identical. Entry of HSV, but not PrV, was blocked by soluble mNectin1delta in NIH 3T3 and L cells. Two features were unexpected. First, soluble mNectin1delta failed to physically interact with HSV glycoprotein D (gD) at a detectable level, although it interacted physically with virions. Second, coexpression of mNectin1delta and HSV gD did not restrict HSV or PrV infection, whereas coexpression of hNectin and gD did restrict infection, suggesting that mNectin1delta fails to be sequestered by HSV gD. We conclude that mNectin1delta serves as a species-nonspecific mediator for entry of the human and animal alphaherpesviruses. This activity, at least for HSV, is independent of a detectable binding to gD.
- Published
- 2000
30. CD68+cells of monocyte/macrophage lineage in the environment of AIDS-associated and classic-sporadic Kaposi sarcoma are singly or doubly infected with human herpesviruses 7 and 6B
- Author
-
Gabriella Campadelli-Fiume, N. Wey, Elisa Avitabile, V. Adams, R. Moos, Werner Kempf, M. Schmid, Kempf W., Adams V., Wey N., Moos R., Schmid M., Avitabile E., and Campadelli-Fiume G.
- Subjects
Male ,Herpesvirus 6, Human ,viruses ,Herpesvirus 7, Human ,Polymerase Chain Reaction ,Monocytes ,Antigen ,medicine ,Humans ,Macrophage ,Cell Lineage ,Sarcoma, Kaposi ,Acquired Immunodeficiency Syndrome ,Multidisciplinary ,biology ,Herpesvirus 6, Human/*isolation & purification Herpesvirus 7, Human/*isolation & purification Humans Immunohistochemistry Male Monocytes/*virology Polymerase Chain Reaction Sarcoma, Kaposi/etiology/*pathology/*virology ,CD68 ,Monocyte ,virus diseases ,Viral tegument ,Biological Sciences ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Immunohistochemistry ,Virology ,medicine.anatomical_structure ,Phosphoprotein ,biology.protein ,Sarcoma ,Antibody - Abstract
Earlier studies have shown that Kaposi sarcomas contain cells infected with human herpesvirus (HHV) 6B, and in current studies we report that both AIDS-associated and classic-sporadic Kaposi sarcoma contain HHV-7 genome sequences detectable by PCR. To determine the distribution of HHV-7-infected cells relative to those infected with HHV-6, sections from paraffin-embedded tissues were allowed to react with antibodies to HHV-7 virion tegument phosphoprotein pp85 and to HHV-6B protein p101. The antibodies are specific for HHV-7 and HHV-6B, respectively, and they retained reactivity for antigens contained in formalin-fixed, paraffin-embedded tissue samples. We report that (i) HHV-7 pp85 was present in 9 of 32 AIDS-associated Kaposi sarcomas, and in 1 of 7 classical-sporadic HIV-negative Kaposi sarcomas; (ii) HHV-7 pp85 was detected primarily in cells bearing the CD68 marker characteristic of the monocyte/macrophage lineage present in or surrounding the Kaposi sarcoma lesions; and (iii) in a number of Kaposi sarcoma specimens, tumor-associated CD68+monocytes/macrophages expressed simultaneously antigens from both HHV-7 and HHV-6B, and therefore appeared to be doubly infected with the two viruses. CD68+monocytes/macrophages infected with HHV-7 were readily detectable in Kaposi sarcoma, but virtually absent from other normal or pathological tissues that harbor macrophages. Because all of the available data indicate that HHV-7 infects CD4+T lymphocytes, these results suggest that the environment of the Kaposi sarcoma (i) attracts circulating peripheral lymphocytes and monocytes, triggers the replication of latent viruses, and thereby increases the local concentration of viruses, (ii) renders CD68+monocytes/macrophages susceptible to infection with HHV-7, and (iii) the combination of both events enables double infections of cells with both HHV-6B and HHV-7.
- Published
- 1997
31. Selection of a monoclonal antibody specific for variant B human herpesvirus 6-infected mononuclear cells
- Author
-
Elisa Avitabile, Gabriella Campadelli-Fiume, Laura Foà-Tomasi, Foa-tomasi L., Avitabile E., and Campadelli-fiume G.
- Subjects
medicine.drug_class ,viruses ,Human herpesvirus 6 ,Herpesvirus 6, Human ,Spleen ,Antibodies, Viral ,Monoclonal antibody ,Immunofluorescence ,Peripheral blood mononuclear cell ,Mice ,Affinity chromatography ,Antibody Specificity ,Virology ,medicine ,Animals ,Humans ,Hybridomas ,Variant B human herpesvirus 6 ,biology ,medicine.diagnostic_test ,Antibodies, Monoclonal ,Proteins ,virus diseases ,biology.organism_classification ,Molecular biology ,Molecular Weight ,medicine.anatomical_structure ,Monoclonal antibody derivation ,Monoclonal ,Leukocytes, Mononuclear ,biology.protein ,Antibody - Abstract
A monoclonal antibody, designated as MAb 6E2, specific for human herpesvirus 6 variant B (HHV-6B) was derived from the spleen of a mouse immunized with lysates of HHV-6B(Z29) cord blood mononuclear cells. MAb 6E2 reacts by immunofluorescence with all the HHV-6B strains tested (Z29, CV, Hashimoto and SF) and fails to react with variant A prototypes, GS and U1102. The immunofluorescence staining was punctate and localized to the cytoplasm. The protein reacting with MAb 6E2 was identified as protein 48 000 in apparent Mr value by immunoaffinity chromatography of lysates of HHV-6B-infected mononuclear cells. © 1995.
- Published
- 1995
32. Viral and cellular contributions to herpes simplex virus entry into the cell
- Author
-
Elisa Avitabile, Gabriella Campadelli-Fiume, Tatiana Gianni, Laura Menotti, Campadelli-Fiume G., Menotti L., Avitabile E., and Gianni T.
- Subjects
Simplexvirus/genetic ,VIRAL ENVELOPE PROTEINS/GENETICS ,viruses ,Biology ,medicine.disease_cause ,Virus ,Herpes Simplex/metabolism ,Viral Envelope Proteins ,Viral entry ,Herpes Simplex/genetic ,Virology ,medicine ,Animals ,Humans ,Simplexvirus ,chemistry.chemical_classification ,Animal ,Herpes Simplex ,Viral tegument ,Virus Internalization ,Herpesvirus glycoprotein B ,Herpes simplex virus ,Capsid ,chemistry ,Cytoplasm ,Herpes Simplex/virology ,Viral Envelope Proteins/metabolism ,Glycoprotein ,SIMPLEXVIRUS/PHYSIOLOGY ,Human - Abstract
Herpes simplex virus (HSV) entry into the cell involves the fusion of the virion envelope with a cellular membrane and delivery of capsid and tegument proteins to the cytoplasm. Our understanding of this phenomenon has greatly increased in recent years. On the virus side, the multipartite nature of the entry-fusion machinery (made of the glycoproteins gD, the heterodimer gH/gL and gB) entails a mechanism of gD activation promoted by the gD encounter with one of its receptor; and cross-talk among the entry-fusion glycoproteins, which culminates in gB activation and fusion execution. On the cell side, machineries and signalling activities are put in place. The number of known receptors and sentinels is increasing. The cell routes the virus through alternative entry pathways by means of routing factors, exemplified by αVβ3-integrin and paired immunoglobulin-like type 2 receptor alpha. Of the signalling events, a key one is the immediate host response to incoming virions. Unexpectedly, this is in part triggered by the same virion components and some cellular factors that also promote virus entry. Hence, a link is emerging between two phenomena so far considered as distinct.
- Published
- 2011
33. Cross Talk among the Glycoproteins Involved in Herpes Simplex Virus Entry and Fusion: the Interaction between gB and gH/gL Does Not Necessarily Require gD▿
- Author
-
Elisa Avitabile, Gabriella Campadelli-Fiume, Cristina Forghieri, Avitabile E, Forghieri C, and Campadelli-Fiume G.
- Subjects
Yellow fluorescent protein ,VIRAL ENVELOPE PROTEINS/GENETICS ,Immunology ,Biology ,medicine.disease_cause ,Microbiology ,Membrane Fusion ,SIMPLEXVIRUS*/GENETICS ,Green fluorescent protein ,Cell Line ,Viral Envelope Proteins ,Protein-fragment complementation assay ,Virology ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Simplexvirus ,Glycoproteins ,chemistry.chemical_classification ,COS cells ,Lipid bilayer fusion ,Virus Internalization ,Molecular biology ,Herpesvirus glycoprotein B ,Genome Replication and Regulation of Viral Gene Expression ,Herpes simplex virus ,chemistry ,GLYCOPROTEINS/GENETICS ,Insect Science ,COS Cells ,biology.protein ,Glycoprotein - Abstract
The gD, gB, and gH/gL glycoprotein quartet constitutes the basic apparatus for herpes simplex virus (HSV) entry into the cell and fusion. gD serves as a receptor binding glycoprotein and trigger of fusion. The conserved gB and gH/gL execute fusion. Central to understanding HSV entry/fusion has become the dissection of how the four glycoproteins engage in cross talk. While the independent interactions of gD with gB and gD with gH/gL have been documented, less is known of the interaction of gB with gH/gL. So far, this interaction has been detected only in the presence of gD by means of a split green fluorescent protein complementation assay. Here, we show that gB interacts with gH/gL in the absence of gD. The gB-gH/gL complex was best detected with a form of gB in which the endocytosis and phosphorylation motif have been deleted; this form of gB persists in the membranes of the exocytic pathway and is not endocytosed. The gB-gH/gL interaction was detected both in whole transfected cells by means of a split yellow fluorescent protein complementation assay and, biochemically, by a pull-down assay. Results with a panel of chimeric forms of gB, in which portions of the glycoprotein bracketed by consecutive cysteines were replaced with the corresponding portions from human herpesvirus 8 gB, favor the view that gB carries multiple sites for interaction with gH/gL, and one of these sites is located in the pleckstrin-like domain 1 carrying the bipartite fusion loop.
- Published
- 2009
34. Herpes simplex virus (HSV) glycoprotein h is partially processed in a cell line that expresses the glycoprotein and fully processed in cells infected with deletion or is mutants in the known hsv glycoproteins
- Author
-
Franca Serafini-Cessij, Roberto Manservigi, Rita Gualandri, Renato Brandimarti, Elisa Avitabile, Laura Foà-Tomasi, Ambra Boscaro, Fabio Dall'olioj, Gabriella Campadelli Fiume, Foa-Tomasi L., Avitabile E., Boscaro A., Brandimarti R., Gualandri R., Manservigi R., Dall'olioj F., Serafini-Cessij F., and Campadelli Fiume G.
- Subjects
Animals Cell Line Chromosome Deletion Genes, Viral Mannose/metabolism *Mutation Oligosaccharides/isolation & purification Plasmids Protein Processing, Post-Translational Recombinant Proteins/biosynthesis/isolation & purification Recombination, Genetic Restriction Mapping Simplexvirus/*genetics Vero Cells Viral Envelope Proteins/biosynthesis/*genetics/isolation & purification ,Genes, Viral ,Viral protein ,Restriction Mapping ,Mutant ,Oligosaccharides ,Biology ,medicine.disease_cause ,Virus ,Cell Line ,symbols.namesake ,Viral Envelope Proteins ,Virology ,medicine ,Animals ,Simplexvirus ,Vero Cells ,Recombination, Genetic ,chemistry.chemical_classification ,Golgi apparatus ,Herpesvirus glycoprotein B ,Molecular biology ,Recombinant Proteins ,Herpes simplex virus ,chemistry ,Cell culture ,Mutation ,symbols ,Chromosome Deletion ,Glycoprotein ,Mannose ,Protein Processing, Post-Translational ,Plasmids - Abstract
Cell lines that constitutively express herpes simplex virus 1 (HSV-1) glycoprotein H (gH-1 ) failed to synthesize the mature form of gH and accumulated a precursor-like form of the glycoprotein, which was retained intracellularly, most likely in RER. Fine-structure analysis of the oligosaccharides present in recombinant gH revealed oligosaccharides processed by RER enzymes; sialylated complex-type and biantennary oligosaccharides, which are assembled in the trans-Golgi, were absent. A small fraction had the characteristics of oligosaccharides processed by the early mannosidases of the Golgi. These findings suggest that a defect in the transport out of RER to the Golgi may account for the intracellular retention of the immature form of gH in cells that express the glycoprotein constitutively. Upon superinfection of cells expressing gH-1 with HSV-2, recombinant gH-1 underwent maturation, indicating that a viral function is required to attain full processing of gH. The known HSV glycoproteins do not appear to carry out this function, since in cells infected with deletion mutants in gD, gG, gE, and gE-gl, with a spontaneous gC- mutant, or with a temperature-sensitive mutant in gB, maturation of gH occurred independently of the presence or of the maturation of the single glycoproteins tested. The present findings together with previous observations on HSV, human CMV, and the EBV homologue of gH suggest that inability of gH to undergo full processing in the absence of viral protein (s) is a property of gH.
- Published
- 1991
35. The multipartite system that mediates entry of herpes simplex virus into the cell
- Author
-
Cristina Forghieri, Gabriella Campadelli-Fiume, Elisa Avitabile, Tatiana Gianni, Michele Amasio, Laura Menotti, Arianna Cerretani, Campadelli-Fiume G., Amasio M., Avitabile E., Cerretani A., Forghieri C., Gianni T, and Menotti L.
- Subjects
chemistry.chemical_classification ,Models, Molecular ,Viral Structural Proteins ,Herpesvirus entry mediator ,Biology ,Virus Internalization ,medicine.disease_cause ,Herpesvirus glycoprotein B ,Virology ,Cell biology ,Multipartite ,Infectious Diseases ,Herpes simplex virus ,Ectodomain ,chemistry ,medicine ,Humans ,Receptors, Virus ,Simplexvirus ,Glycoprotein ,Receptor ,Tropism ,Glycoproteins - Abstract
The multipartite entry-fusion system of herpes simplex virus is made of a quartet of glycoproteins-gD, gB, gH.gL-and three alternative gD receptors, herpesvirus entry mediator (HVEM), nectin1 and modified sites on heparan sulphate. This multipartite system recapitulates the basic steps of virus-cell fusion, i.e. receptor recognition, triggering of fusion and fusion execution. Specifically, in addition to serving as the receptor-binding glycoprotein, gD triggers fusion through a specialised domain, named pro-fusion domain (PFD), located C-terminally in the ectodomain. In the unliganded gD the C-terminal region folds around the N-terminal region, such that gD adopts a closed autoinhibited conformation. In HVEM- and nectin1-bound gD the C-terminal region is displaced (opened conformation). gD is the tool for modification of HSV tropism, through insertion of ligands to heterologous tumour-specific receptors. It is discussed whether gD responds to the interaction with the natural and the heterologous receptors by adopting similar conformations, and whether the closed-to-open switch in conformation is a generalised mechanism of activation. A peculiar recombinant highlighted that the central Ig-folded core of gD may not encode executable functions for entry and that the 219-314 aa segment may be sufficient to trigger fusion. With respect to fusion execution, gB appears to be a prospective fusogen based on its coiled-coil trimeric structure, similar to that of another fusion glycoprotein. On the other hand, gH exhibits molecular elements typical of class 1 fusion glycoproteins, in particular heptad repeats and strong tendency to interact with lipids. Whether fusion execution is carried out by gB or gH.gL, or both glycoproteins in complex or sequentially remains to be determined.
- Published
- 2007
36. Herpes simplex virus glycoprotein K, but not its syncytial allele, inhibits cell-cell fusion mediated by the four fusogenic glycoproteins, gD, gB, gH, and gL
- Author
-
Elisa Avitabile, Gabriella Campadelli-Fiume, Giulia Lombardi, Avitabile E., Lombardi G., and Campadelli-Fiume G.
- Subjects
viruses ,Immunology ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Microbiology ,Giant Cells ,Membrane Fusion ,Cell Line ,herpes simplex virus type 1 (HSV-1), glycoprotein K (gK), cell-cell fusion, fusogenic glycoproteins ,Cell Fusion ,Viral Proteins ,Viral Envelope Proteins ,Virology ,Cricetinae ,Chlorocebus aethiops ,Baby hamster kidney cell ,medicine ,Animals ,Humans ,Vero Cells ,Alleles ,chemistry.chemical_classification ,Syncytium ,Cell fusion ,Lipid bilayer fusion ,Molecular biology ,Herpesvirus glycoprotein B ,Virus-Cell Interactions ,Herpes simplex virus ,chemistry ,Insect Science ,Vero cell ,Glycoprotein - Abstract
A Myc epitope was inserted at residue 283 of herpes simplex virus type 1 (HSV-1) glycoprotein K (gK), a position previously shown not to interfere with gK activity. The Myc-tagged gK localized predominantly to the endoplasmic reticulum, both in uninfected and in HSV-infected cells. gK, coexpressed with the four HSV fusogenic glycoproteins, gD, gB, gH, and gL, inhibited cell-cell fusion. The effect was partially dose dependent and was observed both in baby hamster kidney (BHK) and in Vero cells, indicating that the antifusion activity of gK may be cell line independent. The antifusion activity of gK did not require viral proteins other than the four fusogenic glycoproteins. A syncytial ( syn ) allele of gK ( syn -gK) carrying the A40V substitution present in HSV-1(MP) did not block fusion to the extent seen with the wild-type (wt) gK, indicating that the syn mutation ablated, at least in part, the antifusogenic activity of wt gK. We conclude that gK is part of the mechanism whereby HSV negatively regulates its own fusion activity. Its effect accounts for the notion that cells infected with wt HSV do not fuse with adjacent, uninfected cells into multinucleated giant cells or syncytia. gK may also function to preclude fusion between virion envelope and the virion-encasing vesicles during virus transport to the extracellular compartment, thus preventing nucleocapsid de-envelopment in the cytoplasm.
- Published
- 2003
37. Protection by herpes simplex virus glycoprotein D against Fas-mediated apoptosis - Role of nuclear factor kappa B
- Author
-
M Antonietta, Medici, M Teresa, Sciortino, Donata, Perri, Carla, Amici, Elisa, Avitabile, Marco, Ciotti, Emanuela, Balestrieri, Enrico, De Smaele, Guido, Franzoso, Antonio, Mastino, Medici M.A., Sciortino M.T., Perri D., Amici C., Avitabile E., Ciotti M., Balestrieri E., De Smaele E., Franzoso G., and Mastino A.
- Subjects
Time Factors ,BLOCKS APOPTOSIS ,Ultraviolet Rays ,viruses ,Blotting, Western ,Apoptosis ,Transfection ,INDUCED CELL-DEATH ,HUMAN HEP-2 CELLS ,TRANSCRIPTION FACTORS ,ENTRY MEDIATOR ,MONOCLONAL-ANTIBODIES ,FUNCTIONAL REGION ,PROTEIN-KINASE ,TYPE-1 ,ACTIVATION ,Mice ,NF-KappaB Inhibitor alpha ,Viral Envelope Proteins ,In Situ Nick-End Labeling ,Animals ,Humans ,fas Receptor ,Genes, Dominant ,Caspase 8 ,Dose-Response Relationship, Drug ,NF-kappa B ,U937 Cells ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Caspase 9 ,Coculture Techniques ,Up-Regulation ,Kinetics ,Caspases ,Mutation ,herpes simplex virus glycoprotein D, gD, Fas-mediated apoptosis, nuclear factor κB Caspase 8 Caspase 9 I-kappa B Proteins/metabolism NF-KappaB Inhibitor alpha NF-kappa B/metabolism/*physiology U937 Cells Viral Envelope Proteins/metabolism/*physiology fas Receptor/*metabolism ,Electrophoresis, Polyacrylamide Gel ,I-kappa B Proteins - Abstract
Signals involved in protection against apoptosis by herpes simplex virus 1 (HSV-1) were investigated. Using U937 monocytoid cells as an experimental model, we have demonstrated that HSV-1 rendered these cells resistant to Fas-induced apoptosis promptly after infection. UV-inactivated virus as well as the envelope glycoprotein D (gD) of HSV-1, by itself, exerted a protective effect on Fas-induced apoptosis. NF-kappaB was activated by gD, and protection against Fas-mediated apoptosis by gD was abolished in cells stably transfected with a dominant negative mutant I-kappaBalpha, indicating that NF-kappaB activation plays a role in the antiapoptotic activity of gD in our experimental model. Moreover, NF-kappaB-dependent protection against Fas-mediated apoptosis was associated with decreased levels of caspase-8 activity and with the up-regulation of intracellular antiapoptotic proteins.
- Published
- 2003
38. Retinoids and cancer: antitumoral effects of ATRA, 9-cis RA and the new retinoid IIF on the HL-60 leukemic cell line
- Author
-
Marina Orlandi, K. Ammar, Elisa Avitabile, P. Dal Monte, G. Bartolini, B. Mantovani, Orlandi M., Mantovani B., Ammar K., Avitabile E., Dal Monte P., and Bartolini G.
- Subjects
Transcription, Genetic ,Receptors, Retinoic Acid ,Retinoic acid ,Antineoplastic Agents ,Apoptosis ,HL-60 Cells ,Tretinoin ,DNA Fragmentation ,Retinoid X receptor ,Biology ,Retinoic acid-inducible orphan G protein-coupled receptor ,Retinoids ,chemistry.chemical_compound ,Animals ,Humans ,IIF ,Cancer ,Leukemia ,Retinoid X receptor alpha ,Dose-Response Relationship, Drug ,organic chemicals ,General Medicine ,Phenanthrenes ,Retinoid X receptor gamma ,Retinoic acid receptor ,HL-60 ,Biochemistry ,chemistry ,Proto-Oncogene Proteins c-bcl-2 ,Retinoic acid receptor alpha ,Cancer research ,Retinoid X receptor beta - Abstract
Objective: To compare the antitumoral effects of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) with those of 5-OH,11-O-hydrophenanthrene (IIF), a new derivative of retinoic acid. Materials and Methods: The effect of retinoids was tested on cell line HL-60. Cell differentiation and apoptosis were evaluated by morphological and biochemical analysis as bcl-2 protein and by DNA fragmentation assay. The ability to activate retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) and to modulate gene expression was determined by transactivation assay. Results: With cell line HL-60, the antiproliferative effect of IIF was stronger than that of ATRA and 9-cis RA. Following retinoid treatment, cells appeared to differentiate and apoptotic cells were observed. The appearance of DNA laddering and a decrease in the amount of bcl-2 protein confirmed apoptosis. IIF transcriptionally activated RXR-γ more than RAR-α. Conclusion: The findings indicate that IIF transcriptionally activates RXR-γ preferentially, induces apoptosis and has a more antiproliferative activity than ATRA and 9-cis RA on cell line HL-60.
- Published
- 2001
39. Novel, soluble isoform of the herpes simplex virus (HSV) receptor nectin1 (or PRR1-HIgR-HveC) modulates positively and negatively susceptibility to HSV infection
- Author
-
Gabriella Campadelli-Fiume, Francesca Cocchi, Elisa Avitabile, Patrice Dubreuil, Marc Lopez, Annouck Leclerc, José Adélaïde, Lopez M., Cocchi F., Avitabile E., Leclerc A., Adelaide J., Campadelli-Fiume G., and Dubreuil P.
- Subjects
viruses ,Immunology ,Molecular Sequence Data ,Nectins ,Biology ,medicine.disease_cause ,Microbiology ,Cell Line ,Amino Acid Sequence Animals Base Sequence Cell Adhesion Molecules/genetics/*metabolism Cell Line Cloning, Molecular Culture Media Herpes Simplex/*immunology/virology Humans Molecular Sequence Data Nectins Protein Isoforms/metabolism Receptors, Virus/*metabolism Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA Simplexvirus/*pathogenicity Solubility ,Virology ,Complementary DNA ,medicine ,Animals ,Humans ,Protein Isoforms ,Simplexvirus ,Amino Acid Sequence ,Cloning, Molecular ,Receptor ,Infectivity ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Alternative splicing ,Herpes Simplex ,Transfection ,Sequence Analysis, DNA ,Molecular biology ,Culture Media ,Virus-Cell Interactions ,Herpes simplex virus ,Ectodomain ,Solubility ,Cell culture ,Insect Science ,Receptors, Virus ,Cell Adhesion Molecules - Abstract
A novel member of the nectin family, nectin1γ, was molecularly cloned. The cDNA has the same ectodomain as nectin1α and nectin1β, the two known transmembrane isoforms that serve as receptors for herpes simplex virus (HSV) entry into human cell lines (nectin1α and nectin1β, also called PRR1-HveC and HIgR, respectively). The 1.4-kb transcript, which originated by alternative splicing, is expressed in human cell lines, and appears to have a narrow distribution in human tissues. The sequence does not have a hydrophobic anchoring region, and the protein is secreted in the culture medium of cells transfected with the cDNA. Nectin1γ, purified from culture medium, can compete with membrane-bound nectin1β and reduce HSV infectivity. The expression of nectin1γ cDNA in cells resistant to HSV infection and lacking HSV receptors enables HSV to enter the cell, which implies that it is present at the cell surface. Thus, nectin1γ has the potential both to mediate and to reduce HSV entry into cells.
- Published
- 2001
40. Comparison of murine and human nectin1 binding to herpes simplex virus glycoprotein D (gD) reveals a weak interaction of murine nectin1 to gD and a gD-dependent pathway of entry
- Author
-
Elisa Avitabile, Laura Menotti, Marc Lopez, Patrice Dubreuil, Gabriella Campadelli-Fiume, Menotti L., Avitabile E., Dubreuil P., Lopez M., and Campadelli-Fiume G.
- Subjects
medicine.drug_class ,Mutant ,Nectins ,Animals Antibodies, Monoclonal Binding, Competitive Biotinylation Cell Adhesion Molecules/*metabolism Cell Line Enzyme-Linked Immunosorbent Assay Humans Mice Nectins Precipitin Tests Protein Binding Protein Isoforms/metabolism Receptors, Virus/*metabolism Sequence Deletion Simplexvirus/chemistry/genetics/*metabolism/physiology Solubility Viral Envelope Proteins/genetics/*metabolism Virion/chemistry/genetics/metabolism ,Enzyme-Linked Immunosorbent Assay ,Biology ,medicine.disease_cause ,Monoclonal antibody ,Binding, Competitive ,Virus ,Cell Line ,Mice ,Viral Envelope Proteins ,Virology ,medicine ,Glycoprotein D ,Animals ,Humans ,Protein Isoforms ,Simplexvirus ,Biotinylation ,Receptor ,Sequence Deletion ,Virion ,Antibodies, Monoclonal ,Ligand (biochemistry) ,Molecular biology ,Precipitin Tests ,Herpes simplex virus ,Solubility ,biology.protein ,Receptors, Virus ,Antibody ,Cell Adhesion Molecules ,Protein Binding - Abstract
The murine nectin1alpha (mNectin1alpha), a homolog of human nectin1alpha (hNectin1alpha, or PRR1, HveC), mediates the entry of herpes simplex virus (HSV) into cells. Previously, we reported that the binding of hNectin1 to HSV glycoprotein D (gD) was readily detectable, whereas the binding of mNectin1 to gD was not detectable, thus raising the question whether mNectin1 mediates a gD-dependent or a gD-independent pathway of entry. Here we report comparative binding studies of murine- and human-nectin1alpha to virions and to gD. The assays consistently showed either a very weak binding or no detectable binding of murine nectin1alpha to gD. They included (i) binding of soluble mNectin1-Fc or hNectin1-Fc to virions and competition of the binding by soluble gD(Delta290-299t) and by monoclonal antibodies to gD; (ii) pull-down experiments of wt gD from lysates of infected cells; and (iii) ELISA binding of soluble gD(Delta290-299t) to cells expressing mNectin1 or hNectin1. In contrast to the binding studies, the entry studies readily showed that entry mediated by mNectin1 was dependent on gD. Thus, a gDnull (gD-/-) mutant virus was unable to enter mNectin1-expressing cells, and entry of wild-type virus was inhibited by antibodies to gD or soluble gD at similar concentrations. We infer that gD represents a weak ligand in the interaction between mNectin1 and virions, whereas it represents a strong and the major ligand for hNectin1. Yet gD is required in HSV-1 entry mediated by mNectin1alpha. We conclude that a high-affinity binding of the receptor to gD is not a requirement in the gD-dependent pathway of HSV entry to cells.
- Published
- 2001
41. Nectin2α (PRR2α or HveB) and nectin2δ are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D
- Author
-
Patrice Dubreuil, Elisa Avitabile, Gabriella Campadelli-Fiume, Marc Lopez, Francesca Cocchi, Laura Menotti, Lopez M., Cocchi F., Menotti L., Avitabile E., Dubreuil P., and Campadelli-Fiume G.
- Subjects
Herpesvirus entry mediator ,Proline ,Amino Acid Substitution Antibodies, Monoclonal/immunology Cell Adhesion Molecules/chemistry/immunology/*metabolism Cell Line Herpesvirus 1, Human/genetics/*metabolism Humans Leucine Mutation Nectins Proline Protein Isoforms Protein Structure, Tertiary Receptors, Virus/*metabolism Transfection Viral Envelope Proteins/*genetics ,viruses ,Immunology ,Mutant ,Nectins ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Transfection ,Microbiology ,Cell Line ,Viral Envelope Proteins ,Viral entry ,Leucine ,Virology ,medicine ,Humans ,Protein Isoforms ,education ,education.field_of_study ,HERPESVIRUS ENTRY MEDIATOR B ,Antibodies, Monoclonal ,Molecular biology ,Virus-Cell Interactions ,Protein Structure, Tertiary ,Herpes simplex virus ,Ectodomain ,Amino Acid Substitution ,Insect Science ,Mutation ,Immunoglobulin superfamily ,Receptors, Virus ,Cell Adhesion Molecules - Abstract
The receptors for entry of herpes simplex viruses 1 and 2 (HSV-1 and -2), widely expressed in human cell lines, are members of a subset of the immunoglobulin superfamily exemplified by herpesvirus entry mediator C (HveC) and the herpesvirus immunoglobulin-like receptor (HIgR). This report focuses on two members of this subset, herpesvirus entry mediator B (HveB), recently designated nectin2/PRR2α, and its splice variant isoform, nectin2/PRR2δ. Nectin2α and -δ share the ectodomain but differ in the transmembrane and cytoplasmic regions. HveB was reported to enable entry of HSV-1 carrying mutations in glycoprotein D (gD) and of HSV-2, but not of wild-type (wt) HSV-1. We report that (i) both nectin2α and -δ served as receptors for the entry of HSV-1 mutant viruses HSV-1(U10) and -(U21) and AP7 r that carry the Leu25Pro substitution in gD but not for HSV-1 mutants U30 and R5000 that carry the Ser140 or Ala185 substitution in gD. All of these mutants were able to overcome the block to entry mediated by expression of wt gD. (ii) Infection of cells expressing nectin2α or -δ required exposure to multiplicities of infection about 100-fold higher than those required to infect cells expressing HveC or HIgR. (iii) gD from HSV-1(U21) bound in vitro soluble forms of nectin2. The association was weaker than that to the soluble form of HveC/HIgR. Binding of wt HSV-1 gD to soluble nectin2 was not detectable. (iv) A major region of nectin2 functional in virus entry mapped to the V domain, located at the N terminus.
- Published
- 2000
42. Redistribution of microtubules and Golgi apparatus in herpes simplex virus-infected cells and their role in viral exocytosis
- Author
-
P L Ward, Bernard Roizman, Elisa Avitabile, S Di Gaeta, Gabriella Campadelli-Fiume, Maria Rosaria Torrisi, Avitabile E., Di Gaeta S., Torrisi M.R., Ward P.L., Roizman B., and Campadelli-Fiume G.
- Subjects
Time Factors ,Paclitaxel ,viruses ,Immunology ,Fluorescent Antibody Technique ,Golgi Apparatus ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Kidney ,Virus Replication ,Microbiology ,Coatomer Protein ,Microtubules ,Exocytosis ,Virus ,Cell Line ,symbols.namesake ,chemistry.chemical_compound ,Mice ,Antibodies, Monoclonal Cell Line Chlorocebus aethiops Coatomer Protein Cricetinae Exocytosis Fluorescent Antibody Technique Golgi Apparatus/drug effects/*physiology/ultrastructure Herpesvirus 1, Human/pathogenicity/*physiology Humans Kidney Kinetics Membrane Proteins/analysis Mice/immunology Microscopy, Electron Microtubule-Associated Proteins/analysis Microtubules/drug effects/*physiology/ultrastructure Nocodazole/pharmacology Paclitaxel/pharmacology Time Factors Tubulin/analysis Tumor Cells, Cultured Vero Cells Virus Replication ,Microtubule ,Tubulin ,Virology ,Cricetinae ,Chlorocebus aethiops ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Vero Cells ,Nocodazole ,Antibodies, Monoclonal ,Membrane Proteins ,Golgi apparatus ,Cell biology ,Kinetics ,Microscopy, Electron ,Herpes simplex virus ,chemistry ,Cell culture ,Insect Science ,symbols ,Viral exocytosis ,Microtubule-Associated Proteins ,Research Article - Abstract
Earlier studies have shown that the Golgi apparatus was fragmented and dispersed in herpes simplex virus 1-infected Vero and HEp-2 cells but not in human 143TK- cells, that the fragmentation and dispersal required viral functions expressed concurrently with or after the onset of DNA synthesis (G. Campadelli-Fiume, R. Brandimarti, C. Di Lazzaro, P. L. Ward, B. Roizman, and M. R. Torrisi, Proc. Natl. Acad. Sci. USA 90:2798-2802, 1993), and that in 143TK- cells, but not Vero or HEp-2 cells, infected with viral mutants lacking the UL20 gene virions were glycosylated and transported to extracellular space (J. D. Baines, P. L. Ward, G. Campadelli-Fiume, and B. Roizman, J. Virol. 65:6414-6424, 1991; E. Avitabile, P. L. Ward, C. Di Lazzaro, M. R. Torrisi, B. Roizman, and G. Campadelli-Fiume, J. Virol. 68:7397-7405, 1994). Experiments designed to elucidate the role of the microtubules and of intact or fragmented Golgi apparatus in the exocytosis of virions showed the following. (i) In all cell lines tested (Vero, 143TK-, BHK, and Hep-2) microtubules underwent fragmentation particularly evident at the cell periphery and then reorganized into bundles which circumvent the nucleus. This event was not affected by inhibitors of viral DNA synthesis. We conclude that redistribution of microtubules may be required but is not sufficient for the fragmentation and dispersal of the Golgi apparatus. (ii) In all infected cell lines tested, nocodazole caused fragmentation and dispersal of the Golgi and a far more extensive depolymerization of the microtubules than was seen in untreated, infected Vero or HEp-2 cells. Taxol precluded the depolymerization of the microtubules and fragmentation of the Golgi in both infected cell lines. Neither nocodazole nor taxol affected the exocytosis of infectious virus from Vero, HEp-2, or 143TK- cells infected with wild-type virus. We conclude that the effects of nocodazole or of taxol are dominant over the effects of viral infection in the cell lines tested and that viral exocytosis is independent of the organization of microtubules or of the integrity of the Golgi apparatus. Lastly, the data suggest that herpes simplex viruses have evolved an exocytic pathway for which the UL20 protein is a component required in some cells but not others and in which this protein does not merely compensate for the fragmentation and dispersal of the Golgi apparatus.
- Published
- 1995
43. Polyvalent and monoclonal antibodies identify major immunogenic proteins specific for human herpesvirus 7-infected cells and have weak cross-reactivity with human herpesvirus 6
- Author
-
Elisa Avitabile, Gabriella Campadelli-Fiume, Laura Foà-Tomasi, Liu Ke, Foa-Tomasi L., Avitabile E., Ke L., and Campadelli-Fiume G.
- Subjects
Antigenicity ,medicine.drug_class ,Herpesvirus 6, Human ,Blotting, Western ,Enzyme-Linked Immunosorbent Assay ,Herpesvirus 7, Human ,Cross Reactions ,medicine.disease_cause ,Monoclonal antibody ,Antibodies, Viral ,Cross-reactivity ,Herpesviridae ,Virus ,Monocytes ,Mice ,Viral Proteins ,Immune system ,Virology ,medicine ,Animals ,Humans ,Antigens, Viral ,Cells, Cultured ,chemistry.chemical_classification ,biology ,Antibodies, Monoclonal ,biology.organism_classification ,Fetal Blood ,Molecular biology ,Animals *Antibodies, Monoclonal *Antibodies, Viral Antigens, Viral/analysis/*immunology/isolation & purification Blotting, Western/methods Cells, Cultured Cross Reactions Electrophoresis, Polyacrylamide Gel Enzyme-Linked Immunosorbent Assay/methods Female Fetal Blood Herpesvirus 6, Human/*immunology Herpesvirus 7, Human/*immunology Humans Mice/immunology Monocytes Rabbits/immunology Viral Proteins/analysis/*immunology/isolation & purification ,chemistry ,Human herpesvirus 6 ,Electrophoresis, Polyacrylamide Gel ,Female ,Rabbits ,Glycoprotein - Abstract
Hyperimmune rabbit and mouse sera raised to human herpesvirus 7 (HHV-7)-infected cells and an immune human serum identified 20 [35S]methionine-[35S]cysteine-labelled proteins specific for HHV-7-infected cord blood mononuclear cells, ranging in apparent M(r) from 136K to 30K. The major proteins had apparent M(r) values of 121K, 100K, 87K, 85K, 60K, 51K, 46K, 42K, 40K and 36K. The human serum also identified seven [3H]glucosamine-labelled glycoproteins, with apparent M(r) values of 100K, 89K, 82K, 67K, 63K, 53K and 41K. Four monoclonal antibodies (MAbs) specific for HHV7-infected cells were derived. Two reacted with a family of five antigenically related polypeptides (87K, 85K, 70K, 61K and 57K in apparent M(r)), designated as the p85 complex. Two reacted with 121K and 51K M(r) proteins designated as p121 and p51, respectively. Human sera react with high frequency with the p85 complex and to a lesser extent with p121; hence these two proteins appear to be immunodominant for both humans and laboratory animals. The hyperimmune mouse serum and some of the MAbs showed some cross-reactivity with HHV-6A(U1102)- and 6B(Z29)-infected cells. The implications of cross-reactivity with respect to the human immune response to HHV-6 and -7 infections and prevalence analyses are discussed.
- Published
- 1994
44. Localization and putative function of the U(L)20 membrane protein in cells infected with herpes simplex virus 1
- Author
-
Elisa Avitabile, P L Ward, G Campadelli-Fiume, Bernard Roizman, Ward P.L., Campadelli-Fiume G., Avitabile E., and Roizman B.
- Subjects
Immunology ,Molecular Sequence Data ,Golgi Apparatus ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Microbiology ,symbols.namesake ,Viral Proteins ,U(L)20 protein, herpes simplex virus 1, ( HSV), Golgi apparatus fragmentation, β- COP, Vero and I143tk-minus cells ,Virology ,Chlorocebus aethiops ,medicine ,Extracellular ,Animals ,Vero Cells ,Base Sequence ,Vesicle ,Immune Sera ,Virion ,Membrane Proteins ,Golgi apparatus ,Molecular biology ,Cell biology ,Membrane ,Herpes simplex virus ,Membrane protein ,Cytoplasm ,Insect Science ,Vero cell ,symbols ,Electrophoresis, Polyacrylamide Gel ,Rabbits ,Research Article - Abstract
The UL20 protein of herpes simplex virus 1, an intrinsic membrane protein, is required in infected Vero cells in which the Golgi apparatus is fragmented for the transport of virions from the space between the inner and outer nuclear membranes and for the transport of fully processed cell membrane-associated glycoproteins from the trans-Golgi to the plasma membrane. It is not required in the human 143TK- cell line, in which the Golgi apparatus remains intact. We report the following. (i) The UL20 protein was detected in infected cells beginning at 6 h postinfection and was regulated as a gamma 1 gene. (ii) Pulse-chase experiments revealed no detectable alteration in the mobility of the UL20 protein in polyacrylamide gels. (iii) In both infected Vero and infected 143TK- cells, the UL20 protein was detected by immunofluorescence in association with nuclear membranes and in the cytoplasm. Some of the cytoplasmic fluorescence colocalized with beta-COP, a protein associated with Golgi-derived transport vesicles. UL20 protein was present in virions purified from the extracellular space but could not be detected in the plasma membrane. These results are consistent with the hypothesis that UL20 is a component of virion envelopes and membranes of virion transport vesicles and is selectively retained from the latter in a Golgi compartment.
- Published
- 1994
45. Comparative biochemistry of the ubiquinolcytochrome C oxidoreductase (EC 1.10.2.2) isolated from different heart mitochondria
- Author
-
Mauro Degli Esposti, Giampietro Schiavo, G. Lenaz, Mirco Barilli, Cesare Montecucco, Elisa Avitabile, Esposti M.D., Avitabile E., Barilli M., Schiavo G., Montecucco C., and Lenaz G.
- Subjects
Ubiquinol ,Macromolecular Substances ,Physiology ,macromolecular substances ,Reductase ,Biochemistry ,Mitochondria, Heart ,Cofactor ,Electron Transport Complex III ,chemistry.chemical_compound ,Non-competitive inhibition ,Species Specificity ,Oxidoreductase ,Animals ,Molecular Biology ,chemistry.chemical_classification ,Gel electrophoresis ,biology ,Tuna ,Cytochrome c ,Fishes ,General Medicine ,Turtles ,Ducks ,Enzyme ,chemistry ,biology.protein ,Cattle ,Chickens ,Animals Cattle Chickens Ducks Electron Transport Complex III/isolation & purification/*metabolism Fishes Macromolecular Substances Mitochondria, Heart/*enzymology Species Specificity Tuna Turtles - Abstract
1. 1. The ubiquinol-cytochrome c oxidoreductase (bc1 complex, EC 1.10.2.2) has been isolated from the heart mitochondria of beef, chicken, turkey, duck and tuna with an identical procedure. 2. 2. The polypeptide composition of the different complexes, compared using SDS-polyacrylamide gel electrophoresis, shows that the three subunits carrying the prosthetic groups of the enzyme are highly conserved in all species. 3. 3. Also the large subunits I and II (core proteins) and band VI appear to be conserved in structure, while subunits VII and VIIa show a most remarkable structural variation in the various complexes. 4. 4. The steady-state ubiquinol-cytochrome c reductase analysis of the active enzymes indicates that all the bc1 complexes follow essentially a ping-pong mechanism, with the cytochrome c substrate displaying a partial competitive inhibition vs the ubiquinol substrate. 5. 5. The cytochrome c specificity of the reductase activity clearly is different in the various bc1 complexes, whereas the quinol specificity appears to be identical in all the enzymes. © 1986.
- Published
- 1986
46. Individual herpes simplex virus 1 glycoproteins display characteristic rates of maturation from precursor to mature form both in infected cells and in cells that constitutively express the glycoproteins
- Author
-
Elisa Avitabile, Maria Teresa Lombardo, Franca Serafini-Cessi, Laura Foà-Tomasi, Gabriella Campadelli-Fiume, Campadelli-Fiume G., Lombardo M.T., Foa-Tomasi L., Avitabile E., and Serafini-Cessi F.
- Subjects
Phosphonoacetic Acid ,Cancer Research ,Virion morphogenesis ,Immunoprecipitation ,Morphogenesis ,Kidney ,medicine.disease_cause ,Maturation rate ,Herpesviridae ,Virus ,Cell Line ,Viral Envelope Proteins ,Cricetinae ,Virology ,Alphaherpesvirinae ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Simplexvirus ,Herpes simplex viru ,Protein Precursors ,Laryngeal Neoplasms ,Glycoproteins ,chemistry.chemical_classification ,Mesocricetus ,biology ,Fibroblasts ,biology.organism_classification ,Molecular biology ,Herpesvirus glycoprotein B ,Infectious Diseases ,Herpes simplex virus ,chemistry ,Carcinoma, Squamous Cell ,Glycoprotein ,Protein Processing, Post-Translational - Abstract
Pulse-chase experiments in conjunction with quantitative immunoprecipitation have been used to study the time-course of conversion from precursor to mature form of herpes simplex virus 1 glycoproteins C, D and B (gC, gD, and gB). The experimental systems employed were two infected cell lines and cells that constitutively express gD or gB. The relative rates of conversion among the glycoproteins did not vary in the systems used; the rate of maturation of gC was about two-fold higher than that of gD which, in turn, was about one and a half-fold higher than that of gB. Treatment with phosphonoacetate which inhibits viral DNA synthesis and hence virion morphogenesis induced a striking increase in the time course of conversion of immature gC, gD, and gB to fully glycosylated forms when measured late in the infection. The model of HSV glycoproteins maturation as integral components of the virion envelope is discussed. © 1988.
- Published
- 1988
47. Herpes simplex virus glycoprotein D is sufficient to induce spontaneous pH-independent fusion in a cell line that constitutively expresses the glycoprotein
- Author
-
Daniela Stirpe, Minas Arsenakis, Elisa Avitabile, Gabriella Campadelli-Fiume, Bernard Roizman, Sergio Fini, Campadelli-Fiume G., Avitabile E., Fini S., Stirpe D., Arsenakis M., and Roizman B.
- Subjects
Cell Fusion/drug effects Cell Line Concanavalin A/pharmacology Hydrogen-Ion Concentration Immunologic Techniques Neuraminidase/pharmacology Trypsin/pharmacology Viral Envelope Proteins/*physiology Viral Fusion Proteins/*physiology ,Neuraminidase ,medicine.disease_cause ,Virus ,Cell Line ,Cell Fusion ,chemistry.chemical_compound ,Viral Envelope Proteins ,Virology ,medicine ,Concanavalin A ,Trypsin ,Cell fusion ,biology ,Antibodies, Monoclonal ,Hydrogen-Ion Concentration ,Herpesvirus glycoprotein B ,Molecular biology ,Sialic acid ,Herpes simplex virus ,Biochemistry ,chemistry ,Cell culture ,biology.protein ,Immunologic Techniques ,Viral Fusion Proteins - Abstract
Spontaneous small polykaryocytes were detected in a cell line designated BJ-o that harbors the Bam HI J fragment of herpes simplex virus 1 DNA and expresses constitutively glycoprotein D (gD). The fusion activity of BJ-o cells correlated with gD production and was drastically reduced following exposure of the cells to monoclonal antibody HD1 to gD. Studies on the characteristics and requirements of cell fusion dependent on gD led to the conclusion that the characteristics and requirements for gD-mediated fusion activity of BJ-o cells are similar to those previously reported for cell fusion induced by the virus in that (i) polykaryocytosis was not augmented by exposure to medium of low pH with or without prior exposure to trypsin, (ii) the number of polykaryocytes was reduced following removal of terminal sialic acid residues by neuraminidase, and (iii) the number of polykaryocytes was augmented by masking of high-mannose N-linked oligosaccharides with concanavalin A or with its reduced form, succinyl concanavalin A. This effect was reversed by competition with man nose.
- Published
- 1988
48. Glycoprotein D of herpes simplex virus encodes a domain which precludes penetration of cells expressing the glycoprotein by superinfecting herpes simplex virus
- Author
-
Bernard Roizman, Laura Foà-Tomasi, Gabriella Campadelli-Fiume, Renato Brandimarti, Sun Qi, Elisa Avitabile, Campadelli-Fiume G., Qi S., Avitabile E., Foa-Tomasi L., Brandimarti R., and Roizman B.
- Subjects
Genes, Viral ,viruses ,Immunology ,Restriction Mapping ,Viral Plaque Assay ,Biology ,medicine.disease_cause ,Transfection ,Microbiology ,Epitope ,Virus ,Cell Line ,Restriction map ,Viral Envelope Proteins ,Viral entry ,Virology ,medicine ,Baby hamster kidney cell ,Animals ,Simplexvirus ,Virus quantification ,Antibodies, Monoclonal ,Molecular biology ,Herpes simplex virus ,Animals Antibodies, Monoclonal Cell Line DNA, Viral/genetics Genes, Viral Mutation Phenotype Restriction Mapping Simplexvirus/*genetics/isolation & purification Transfection Viral Envelope Proteins/biosynthesis/*genetics/isolation & purification Viral Plaque Assay ,Phenotype ,Insect Science ,DNA, Viral ,Mutation ,Research Article - Abstract
Earlier studies have shown that herpes simplex viruses adsorb to but do not penetrate permissive baby hamster kidney clonal cell lines designated the BJ series and constitutively expressing the herpes simplex virus 1 (HSV-1) glycoprotein D (gD). To investigate the mechanism of the restriction, the following steps were done. First, wild-type HSV-1 strain F [HSV-1(F)] virus was passaged blindly serially on clonal line BJ-1 and mutant viruses [HSV-1(F)U] capable of penetration were selected. The DNA fragment capable of transferring the capacity to infect BJ cells by marker transfer contains the gD gene. The mutant gD, designated gDU, differed from wild-type gD only in the substitution of Leu-25 by proline. gDU reacted with monoclonal antibodies which neutralize virus and whose epitopes encompass known functional domains involved in virus entry into cells. It did not react with the monoclonal antibody AP7 previously shown to react with an epitope which includes Leu-25. Second, cell lines expressing gDU constitutively were constructed and cloned. Unlike the clonal cell lines constitutively expressing gD (e.g., the BJ cell line), those expressing gDU were infectable by both HSV-1(F) and HSV-1(F)U. Lastly, exposure of BJ cells to monoclonal antibody AP7 rendered the cells capable of being infected with HSV-1(F). The results indicate that (i) gD expresses a specific function, determined by sequences at or around Leu-25, which blocks entry of virus into cells synthesizing gD, (ii) the gD which blocks penetration by superinfecting virus is located in the plasma membrane, (iii) the target of the restriction to penetration is the identical domain of the gD molecule contained in the envelope of the superinfecting virus, and (iv) the molecular basis of the restriction does not involve competition for a host protein involved in entry, as was previously thought.
49. Prospective validation of the EASL management algorithm for acute kidney injury in cirrhosis.
- Author
-
Ma AT, Solé C, Juanola A, Escudé L, Napoleone L, Avitabile E, Pérez-Guasch M, Carol M, Pompili E, Gratacós-Ginés J, Soria A, Rubio AB, Cervera M, Moreta MJ, Morales-Ruiz M, Solà E, Poch E, Fabrellas N, Graupera I, Pose E, and Ginès P
- Subjects
- Humans, Male, Female, Prospective Studies, Middle Aged, Aged, Albumins administration & dosage, Vasoconstrictor Agents administration & dosage, Vasoconstrictor Agents therapeutic use, Lypressin analogs & derivatives, Lypressin administration & dosage, Lypressin therapeutic use, Treatment Outcome, Hepatorenal Syndrome etiology, Hepatorenal Syndrome diagnosis, Hepatorenal Syndrome drug therapy, Practice Guidelines as Topic, Algorithms, Acute Kidney Injury etiology, Acute Kidney Injury diagnosis, Liver Cirrhosis complications, Terlipressin administration & dosage
- Abstract
Background & Aims: The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm for the management of AKI, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice., Methods: We performed a prospective cohort study in consecutive hospitalized patients with cirrhosis and AKI. The EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). The primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy., Results: A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in one-third of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with acute tubular necrosis (ATN) being the most common phenotype. The response rate in patients not meeting the criteria for HRS-AKI was 70%. Only 30 patients met the diagnostic criteria for HRS-AKI, and their response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While uNGAL (urinary neutrophil gelatinase-associated lipocalin) could differentiate ATN from other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema., Conclusions: The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy., Impact and Implications: The occurrence of acute kidney injury (AKI) in patients with cirrhosis is associated with poor short-term mortality. Improving its rapid identification and prompt management was the focus of the recently proposed EASL AKI algorithm. This is the first prospective study demonstrating that high AKI response rates are achieved with the use of this algorithm, which includes identification of AKI, treatment of precipitating factors, a 2-day albumin challenge in patients with AKI ≥1B, and supportive therapy in patients with persistent AKI not meeting HRS-AKI criteria or terlipressin with albumin in those with HRS-AKI. These findings support the use of this algorithm in clinical practice., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
50. Protective Mechanisms of Vaginal Lactobacilli against Sexually Transmitted Viral Infections.
- Author
-
Avitabile E, Menotti L, Croatti V, Giordani B, Parolin C, and Vitali B
- Subjects
- Humans, Female, Sexually Transmitted Diseases, Viral immunology, Sexually Transmitted Diseases, Viral prevention & control, Sexually Transmitted Diseases, Viral virology, Microbiota, Lactobacillus physiology, Vagina microbiology, Vagina virology, Vagina immunology
- Abstract
The healthy cervicovaginal microbiota is dominated by various Lactobacillus species, which support a condition of eubiosis. Among their many functions, vaginal lactobacilli contribute to the maintenance of an acidic pH, produce antimicrobial compounds, and modulate the host immune response to protect against vaginal bacterial and fungal infections. Increasing evidence suggests that these beneficial bacteria may also confer protection against sexually transmitted infections (STIs) caused by viruses such as human papillomavirus (HPV), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). Viral STIs pose a substantial public health burden globally, causing a range of infectious diseases with potentially severe consequences. Understanding the molecular mechanisms by which lactobacilli exert their protective effects against viral STIs is paramount for the development of novel preventive and therapeutic strategies. This review aims to provide more recent insights into the intricate interactions between lactobacilli and viral STIs, exploring their impact on the vaginal microenvironment, host immune response, viral infectivity and pathogenesis, and highlighting their potential implications for public health interventions and clinical management strategies.
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.