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2. High HIV-1 diversity in immigrants resident in Italy (2008–2017)

Author

Maggiorella M. T., Sanarico N., Brindicci G., Monno L., Santoro C. R., Coppola N., Cuomo N., Azzurri A., Cesario F., Luciani F., El-Hamad I., D'Ettorre G., Turriziani O., Mazzuti L., Poggi A., Vichi F., Mariabelli E., Surace L., Berardelli G., Picconi O., Cenci A., Sernicola L., Rovetto C., Fulgenzi D., Belli R., Salvi E., Zeo P. D., Borsetti A., Ridolfi B., Losappio R., Zoboli F., Schietroma I., Cella E., Angeletti S., Ciccozzi M., D'Amato S., Ensoli B., Butto S., Angarano G., Babudieri S., Scheri G. C., Lichtner M., Martini S., Mazzella A., Romano N., Pansera A., Pontali E., Raddi A., Starnini G., Dell'Isola S., Maggiorella, M. T., Sanarico, N., Brindicci, G., Monno, L., Santoro, C. R., Coppola, N., Cuomo, N., Azzurri, A., Cesario, F., Luciani, F., El-Hamad, I., D'Ettorre, G., Turriziani, O., Mazzuti, L., Poggi, A., Vichi, F., Mariabelli, E., Surace, L., Berardelli, G., Picconi, O., Cenci, A., Sernicola, L., Rovetto, C., Fulgenzi, D., Belli, R., Salvi, E., Zeo, P. D., Borsetti, A., Ridolfi, B., Losappio, R., Zoboli, F., Schietroma, I., Cella, E., Angeletti, S., Ciccozzi, M., D'Amato, S., Ensoli, B., Butto, S., Angarano, G., Babudieri, S., Scheri, G. C., Lichtner, M., Martini, S., Mazzella, A., Romano, N., Pansera, A., Pontali, E., Raddi, A., Starnini, G., and Dell'Isola, S.

Subjects
0301 basic medicine, Male, Latin Americans, Immigration, Human immunodeficiency virus (HIV), lcsh:Medicine, HIV Infections, Drug resistance, medicine.disease_cause, Antiretroviral Therapy, Highly Active, Cluster Analysis, HIV Infection, lcsh:Science, Phylogeny, media_common, Recombination, Genetic, Multidisciplinary, Geography, virus diseases, High HIV-1 diversity in immigrants, Middle Aged, Italy, Medicine, Infectious diseases, Female, Human, Adult, Tuberculosis, media_common.quotation_subject, Science, 030106 microbiology, Emigrants and Immigrants, Article, 03 medical and health sciences, Population screening, Drug Resistance, Viral, medicine, Humans, Hepatitis, Cluster Analysi, lcsh:R, Genetic Variation, Emigrants and Immigrant, medicine.disease, Antiretroviral therapy, 030104 developmental biology, Mutation, HIV-1, lcsh:Q, Demography, Diversity (politics)
Abstract

The proportion of new diagnoses of HIV infection in immigrants residing in Italy raised from 11% in 1992 to 29.7% in 2018. To investigate the HIV clades circulating in this community a retrospective study was performed in 557 HIV-infected immigrants living in 12 Italian cities. Immigrants originated from East-Europe and Central-Asia (11.7%), North Africa and Middle East (7.3%), South and South-East Asia (7.2%), Latin America and the Caribbean (14.4%), and sub-Saharan Africa (59.4%). More than 87% of immigrants were on antiretroviral therapy (ART), although 26.6% of them were viremic. A 22.0% of immigrants had hepatitis (HBV and/or HCV) and/or tuberculosis. HIV phylogenetic analysis on sequences from 192 immigrants showed the presence of clades B (23.4%), G (16.1%), C (10.4%), A1 (9.4%), F1 (5.2%), D (1.6%) and Circulating Recombinant Forms (CRFs) (33.9%). CRF02_AG represented 72.3% of the total CRFs. Clusters between immigrants and Italian natives were also present. Drug resistance mutations to NRTI, NNRTI, and PI drug classes occurred in 29.1% of ART-treated and in 12.9% of ART-naïve individuals. These data highlight the need for tailored public health interventions in immigrants to avoid spreading in Italy of HIV genetic forms and ART-resistant variants, as well as HIV co-morbidities.

Published
2020

6. Direct detection of proviral gag segment of HIV In peripheral blood lymphocytes by a colorimetric PCR assay as a clinical laboratory tool applied to different at-risk populations

Author

PANE, FABRIZIO, BUTTO S, GOBBO ML, FRANCO M, BUTTERONI C, MAIORANO G, FOGGIA M, CATALDO PT, GUARINO A, TAMBURRINI E, SOLINAS S, PIAZZA M, VECCHIO G, VERANI P, SALVATORE F., PASTORE, LUCIO, Pane, Fabrizio, Butto, S, Gobbo, Ml, Franco, M, Butteroni, C, Pastore, Lucio, Maiorano, G, Foggia, M, Cataldo, Pt, Guarino, A, Tamburrini, E, Solinas, S, Piazza, M, Vecchio, G, Verani, P, and Salvatore, F.

Published
1995

7. Long term protection against SHIV89.6P replication in Tat protein or tat DNA vaccinated cynomolgus monkeys upon tetanus toxoid boost and correlation with Tat immune response

Author

Maggiorella, M. T., Baroncelli, S., Michelini, Z., FANALES BELASIO, E., Moretti, S., Sernicola, L., Cara, A., Butto', S., Fiorelli, V., Tripiciano, A., Caputo, Antonella, Borsetti, A., Negri, D. M., Ridolfi, B., Bona, R., TEN HAAFT, P., Belli, R., Macchia, I., Leone, P., PAVONE COSSUT, M. R., Verani, P., Titti, F., Cafaro, A., and Ensoli, B.

Published
2004

9. Development of HIV/AIDS vaccine based on Tat: preclinical and clinical studies

Author

Cara, A., Cafaro, A., Baroncelli, S., Maggiorella, Mt, Negri, Drm, Fanales-Belasio, E., Moretti, S., Michelini, Z., Fiorelli, V., Butto, S., Tripiciano, A., Sernicola, L., Scoglio, A., Borsetti, A., Ridolfi, B., Iole Macchia, Mancini, Mg, Belli, R., Farcomeni, S., Nappi, F., Vardas, E., Colvin, M., Laguardia, E., Caputo, A., Magnani, M., Titti, F., and Ensoli, B.

Subjects
NO
Published
2002

13. Defective response to T cell mitogens in mice injected with human immunodeficiency virus type 1-infected U937 cells

Author

Ausiello, C. M., primary, Sestili, P., additional, Locardi, C., additional, Logozzi, M., additional, Rizza, P., additional, Parlanti, E., additional, Yang, L.-x., additional, Modica, A., additional, Modesti, A., additional, Musiani, P., additional, Kaido, T. J., additional, Rozera, C., additional, Butto, S., additional, and Belardelli, F., additional

Published
1994
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14. The development of a vaccine against AIDS based on the HIV-1 Tat protein.

Author

Ensoli, B. and Butto, S.

Subjects
*VACCINES, *AIDS vaccines
Abstract

The inexorable spread of the HIV pandemic and mounting deaths from AIDS in developing countries underscore the urgency for an effective vaccine against AIDS. Although many attempts have been made to produce a candidate vaccine of proven efficacy in primates, none is yet available. This is mostly the result of HIV envelope variability and the difficulty of eliciting high titres of long-lasting neutralizing antibodies capable of blocking entry of different virus strains. Thus, sterilizing immunity, although conceptually possible, is not easily achieved. Secondary endpoints in HIV vaccine development are therefore acquiring more importance and leading to the belief that control of viral infection and blocking of disease onset may be a more achievable goal of AIDS vaccine strategies. In this respect, recent attempts to elicit immunity against the HIV regulatory gene product Tat have provided exciting results which open new avenues to obtaining an effective vaccine against HIV infection. [ABSTRACT FROM AUTHOR]

Published
2000

15. DIRECT-DETECTION OF PROVIRAL GAG SEGMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS IN PERIPHERAL-BLOOD LYMPHOCYTES BY COLORIMETRIC PCR ASSAY AS A CLINICAL LABORATORY TOOL APPLIED TO DIFFERENT AT-RISK POPULATIONS

Author

Pane, F., Butto, S., Gobbo, M. L., Franco, M., cinzia butteroni, Pastore, L., Maiorano, G., Foggia, M., Cataldo, P. T., Guarino, A., Tamburrini, E., Solinas, S., Piazza, M., Vecchio, G., Verani, P., Salvatore, F., Pane, Fabrizio, Butto, S., Gobbo, M. L., Franco, M., Butteroni, C., Pastore, Lucio, Maiorano, G., Foggia, M., Cataldo, P. T., Guarino, A., Tamburrini, E., Solinas, S., Piazza, M., Vecchio, Giancarlo, Verani, P., and Salvatore, Francesco

Subjects
PEDIATRIC-PATIENTS, SEQUENCES, HIV-INFECTION, INSITU HYBRIDIZATION, TYPE-1 INFECTION, AMPLIFICATION, DNA, POLYMERASE CHAIN-REACTION, DIAGNOSIS, SPECIMENS
Abstract

We used a colorimetric polymerase chain reaction (PCR)-based assay in kit form to detect directly human immunodeficiency virus type 1 (HIV-1) proviral gag sequences in peripheral blood cells from 68 healthy blood donors, 51 subjects at risk for HIV infection, 122 patients with HIV-1 infection, 11 patients with indeterminate Western blot (immunoblot) results, 4 blood donors HIV-1 positive by enzyme immunoassay, and 13 children born to HIV-1-seropositive mothers. The results obtained in the blood donors and HIV-1-infected patients demonstrated the high degree of diagnostic Specificity and sensitivity of the PCR method. HIV-1 infection was excluded in 10 of the 11 patients with indeterminate Western blot results and in all four enzyme immunoassay-positive blood donors. A diagnosis of HIV infection was ruled out by negative PCR results in 5 of 13 children from seropositive mothers, which excluded vertical transmission of the infection in these cases; these children were younger than 3 months and had positive serological results. Two at-risk patients with negative serological results had positive PCR results. All results were confirmed by conventional PCR. In conclusion, colorimetric PCR, which is commercially available in kit form, is an easy and reliable technique that can be used to detect proviral HIV-1 genomes in blood cells, and despite the limitations owing to HIV genome variability, it is useful in the clinical setting for the diagnosis of HIV infection in selected categories of patients.

29. Development of HIV/AIDS vaccine based on Tat: Preclinical and clinical studies

Author

Cara, A., Cafaro, A., Baroncelli, S., Maggiorella, Mt, Negri, Drm, Fanales-Belasio, E., Moretti, S., Michelini, Z., Fiorelli, V., Butto, S., Tripiciano, A., Sernicola, L., Scoglio, A., Borsetti, A., Barbara Ridolfi, Macchia, I., Mancini, Mg, Belli, R., Farcomeni, S., Nappi, F., Vardas, E., Colvin, M., Laguardia, E., Caputo, A., Magnani, M., Titti, F., Ensoli, B., and MONDUZZI EDITORE

33. A new antigen scanning strategy for monitoring HIV-1 specific T-cell immune responses

Author

Volker Erfle, Guido Poli, Simone Allgayer, Richard H. Glashoff, Paolo Lusso, Peter Reitmeir, Emanuele Fanales-Belasio, Fabrizio Ensoli, Giuseppe Tambussi, Samantha J. Westrop, Nesrina Imami, Mauro S. Malnati, Claudio Fortis, Stefano Buttò, Walter Liebrich, Barbara Ensoli, Silvia Nozza, Antonio Cosma, Harvey Holmes, Silvia Heltai, Antonella Tripiciano, Eftyhia Vardas, Malnati, M, Heltai, S, Cosma, A, Reitmeir, P, Allgayer, S, Glashoff, Rh, Liebrich, W, Vardas, E, Imami, N, Westrop, S, Nozza, S, Tambussi, G, Butto, S, Fanales Belasio, E, Ensoli, B, Ensoli, F, Tripiciano, A, Fortis, C, Lusso, P, Poli, Guido, Erfle, V, and Holmes, H.

Subjects
CD4-Positive T-Lymphocytes, T cell, Molecular Sequence Data, Immunology, Human immunodeficiency virus (HIV), Epitopes, T-Lymphocyte, HIV Infections, CD8-Positive T-Lymphocytes, medicine.disease_cause, Sensitivity and Specificity, Interferon-gamma, Immune system, Antigen, Acquired immunodeficiency syndrome (AIDS), Sequence Analysis, Protein, Humans, Immunology and Allergy, Medicine, Amino Acid Sequence, Antigens, Databases, Protein, AIDS Vaccines, business.industry, ELISPOT, virus diseases, medicine.disease, Virology, Vaccination, CTL, medicine.anatomical_structure, HIV-1, Peptides, business
Abstract

Delineation of the immune correlates of protection in natural infection or after vaccination is a mandatory step for vaccine development. Although the most recent techniques allow a sensitive and specific detection of the cellular immune response, a consensus on the best strategy to assess their magnitude and breadth is yet to be reached. Within the AIDS Vaccine Integrated Project (AVIP http://www.avip-eu.org) we developed an antigen scanning strategy combining the empirical-based approach of overlapping peptides with a vast array of database information. This new system, termed Variable Overlapping Peptide Scanning Design (VOPSD), was used for preparing two peptide sets encompassing the candidate HIV-1 vaccine antigens Tat and Nef. Validation of the VOPSD strategy was obtained by direct comparison with 15mer or 20mer peptide sets in a trial involving six laboratories of the AVIP consortium. Cross-reactive background responses were measured in 80 HIV seronegative donors (HIV-), while sensitivity and magnitude of Tat and Nef-specific T-cell responses were assessed on 90 HIV+ individuals. In HIV-, VOPSD peptides generated background responses comparable with those of the standard sets. In HIV-1+ individuals the VOPSD pools showed a higher sensitivity in detecting individual responses (Tat VOPSD vs. Tat 15mers or 20mers: p

Published
2012
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34. Preparing for phase II/III HIV vaccine trials in Africa

Author

Stefano Buttò, Mario Clerici, Guido Poli, Eftyhia Vardas, Mauro S. Malnati, Richard H. Glashoff, Vardas, E, Butto, S, Glashoff, R, Malnati, M, Poli, Guido, and Clerici, M.

Subjects
medicine.medical_specialty, Immunology, Human immunodeficiency virus (HIV), HIV Infections, Context (language use), medicine.disease_cause, Microbiology, Clinical Trials, Phase II as Topic, Acquired immunodeficiency syndrome (AIDS), medicine, Humans, HIV vaccine, Intensive care medicine, AIDS Vaccines, biology, business.industry, HIV, Cross reactions, medicine.disease, biology.organism_classification, Clinical trial, Infectious Diseases, Clinical Trials, Phase III as Topic, Africa, Lentivirus, Laboratories, business
Abstract

Before performing phase II/III clinical trials in Africa, preliminary studies, including assessment and building up of clinical and laboratory infrastructures, estimates of human immunodeficiency virus incidence, investigation of the background immune response, and evaluation of the cross-clade immune response, need to be done. Plans and ongoing work in the context of the AIDS Vaccine Integrated Project and some preliminary data are presented. (c) 2005 Elsevier SAS. All rights reserved.

Published
2005

35. Containment of infection in tat vaccinated monkeys after rechallenge with a higher dose of SHIV89.6P(cy243).

Author

Borsetti A, Baroncelli S, Maggiorella MT, Moretti S, Fanales-Belasio E, Sernicola L, Tripiciano A, Macchia I, Michelini Z, Belli R, Farcomeni S, Pavone-Cossut MR, Negri D, Caputo A, Bellino S, Butto S, Titti F, Cafaro A, and Ensoli B

Subjects
Animals, CD4 Lymphocyte Count, Cell Proliferation, HIV genetics, HIV Antibodies blood, Humans, Interferon-gamma metabolism, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear virology, Macaca fascicularis, Recombination, Genetic, Simian Acquired Immunodeficiency Syndrome immunology, Simian Immunodeficiency Virus genetics, Viral Load, AIDS Vaccines immunology, HIV immunology, Simian Acquired Immunodeficiency Syndrome prevention & control, Simian Immunodeficiency Virus immunology, tat Gene Products, Human Immunodeficiency Virus immunology
Abstract

We previously reported that cynomolgus monkeys vaccinated with the human immunodeficiency virus (HIV)-1 Tat protein controlled infection after challenge with the simian human immunodeficiency virus (SHIV) 89.6P(cy243) for up to 2 y of follow-up. To evaluate the breadth of the protective immunity elicited by the Tat protein, the vaccines along with the naïve monkeys were intravenously rechallenged with a fivefold higher dose (50 MID(50)) of the same SHIV-89.6P(cy243). The vaccinated monkeys exhibited a statistically significant and long-lasting reduction of viral replication compared to control monkeys. This effect was associated with a strong anamnestic response to Tat, while responses to Gag and Env were nearly undetectable. Taken together, these data provide further evidence for the usefulness of Tat-based vaccines.

Published
2009
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36. HIV-1 Tat-based vaccines: from basic science to clinical trials.

Author

Fanales-Belasio E, Cafaro A, Cara A, Negri DR, Fiorelli V, Butto S, Moretti S, Maggiorella MT, Baroncelli S, Michelini Z, Tripiciano A, Sernicola L, Scoglio A, Borsetti A, Ridolfi B, Bona R, Ten Haaft P, Macchia I, Leone P, Pavone-Cossut MR, Nappi F, Vardas E, Magnani M, Laguardia E, Caputo A, Titti F, and Ensoli B

Subjects
AIDS Vaccines administration & dosage, Animals, CD4-Positive T-Lymphocytes immunology, Clinical Trials as Topic, Gene Products, tat metabolism, HIV-1 metabolism, Macaca fascicularis, South Africa, Th1 Cells immunology, Uganda, tat Gene Products, Human Immunodeficiency Virus, AIDS Vaccines immunology, Gene Products, tat immunology, HIV-1 immunology
Abstract

Vaccination against human immunodeficiency virus (HIV)-1 infection requires candidate antigen(s) (Ag) capable of inducing an effective, broad, and long-lasting immune response against HIV-1 despite mutation events leading to differences in virus clades. The HIV-1 Tat protein is more conserved than envelope proteins, is essential in the virus life cycle and is expressed very early upon virus entry. In addition, both humoral and cellular responses to Tat have been reported to correlate with a delayed progression to disease in both humans and monkeys. This suggested that Tat is an optimal target for vaccine development aimed at controlling virus replication and blocking disease onset. Here are reviewed the results of our studies including the effects of the Tat protein on monocyte-derived dendritic cells (MDDCs) that are key antigen-presenting cells (APCs), and the results from vaccination trials with both the Tat protein or tat DNA in monkeys. We provide evidence that the HIV-1 Tat protein is very efficiently taken up by MDDCs and promotes T helper (Th)-1 type immune responses against itself as well as other Ag. In addition, a Tat-based vaccine elicits an immune response capable of controlling primary infection of monkeys with the pathogenic SHIV89.6P at its early stages allowing the containment of virus spread. Based on these results and on data of Tat conservation and immune cross-recognition in field isolates from different clades, phase I clinical trials are being initiated in Italy for both preventive and therapeutic vaccination.

Published
2002
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37. Immune activation in africa is environmentally-driven and is associated with upregulation of CCR5. Italian-Ugandan AIDS Project.

Author

Clerici M, Butto S, Lukwiya M, Saresella M, Declich S, Trabattoni D, Pastori C, Piconi S, Fracasso C, Fabiani M, Ferrante P, Rizzardini G, and Lopalco L

Subjects
Africa, HIV Antibodies blood, HIV Infections ethnology, HIV Infections virology, HIV Seronegativity immunology, HIV Seropositivity immunology, HIV Seropositivity virology, Humans, Italy, Neutralization Tests, Polymerase Chain Reaction, RNA, Messenger analysis, Receptors, CCR5 genetics, Receptors, CXCR4 analysis, Receptors, CXCR4 genetics, HIV Infections immunology, HIV-1, Receptors, CCR5 analysis
Abstract

Background: HIV infection in Africa is associated with immune activation and a cytokine profile that stimulates CCR5 expression. We investigated whether this immune activation is environmentally driven; if a dominant expression of CCR5 could indeed be detected in African individuals; and if R5 HIV strains would be prevalent in this population., Methods: Freshly drawn peripheral blood mononuclear cells from HIV-uninfected African and Italian individuals living in rural Africa, from HIV-uninfected Africans and Italians living in Italy, and from HIV-infected African and Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virological analyses included virus isolation and characterization of plasma neutralizing activity., Findings: Results showed that: immune activation is detected both in Italian and African HIV-uninfected individuals living in Africa but not in African subjects living in Italy; CCR5-specific mRNA is augmented and the surface expression of CCR5 is increased in African compared with Italian residents (CXCR4-specific mRNA is comparable); R5-HIV strains are isolated prevalently from lymphocytes of African HIV-infected patients; and plasma neutralizing activity in HIV-infected African patients is mostly specific for R5 strains., Conclusions: Immune activation in African residents is environmentally driven and not genetically predetermined. This immune activation results in a skewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isolation of R5 viruses. These data suggest that the selection of the predominant virus strain within the population could be influenced by an immunologically driven pattern of HIV co receptor expression.

Published
2000
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38. Alpha interferon inhibits human herpesvirus 8 (HHV-8) reactivation in primary effusion lymphoma cells and reduces HHV-8 load in cultured peripheral blood mononuclear cells.

Author

Monini P, Carlini F, Stürzl M, Rimessi P, Superti F, Franco M, Melucci-Vigo G, Cafaro A, Goletti D, Sgadari C, Butto' S, Leone P, Chiozzini C, Barresi C, Tinari A, Bonaccorsi A, Capobianchi MR, Giuliani M, di Carlo A, Andreoni M, Rezza G, and Ensoli B

Subjects
Genes, Viral, Herpesvirus 8, Human growth & development, Humans, Interferon alpha-2, Interferon-alpha pharmacology, Leukocytes, Mononuclear virology, Lymphoma, Male, Morphogenesis, Recombinant Proteins, Tetradecanoylphorbol Acetate pharmacology, Tumor Cells, Cultured, Viral Load, Virion, Virus Activation, Herpesvirus 8, Human immunology, Interferon-alpha immunology
Abstract

Infection by human herpesvirus 8 (HHV-8) is associated with the development of Kaposi's sarcoma (KS). Since regression of KS can be achieved by treatment of the patients with alpha interferon (IFN-alpha), we analyzed the effects of IFN-alpha or anti-IFN-alpha antibodies (Ab) on HHV-8 latently infected primary effusion lymphoma-derived cell lines (BCBL-1 and BC-1) and on peripheral blood mononuclear cells (PBMC) from patients with all forms of KS and from at-risk subjects. IFN-alpha inhibited in a dose-dependent manner the amplification of HHV-8 DNA in BCBL-1 cells induced to lytic infection with tetradecanoyl phorbol acetate (TPA). This effect was associated with the inhibition of the expression of HHV-8 nut-1 and kaposin genes that are induced early and several hours, respectively, after TPA treatment. In addition, IFN-alpha inhibited virus production and/or release from BCBL-1 cells. Inhibition of nut-1 and kaposin genes by IFN-alpha was also observed in BC-1 cells induced with n-butyrate. Conversely, the addition of anti-IFN-alpha Ab to TPA-induced BCBL-1 cells resulted in a larger number of mature enveloped particles and in a more extensive cytopathic effect due to the neutralization of the endogenous IFN produced by these cells. IFN was also produced by cultured PBMC from HHV-8-infected individuals, and this was associated with a loss of viral DNA during culture. However, the addition of anti-IFN-alpha Ab or anti-type I IFN receptor Ab promoted the maintenance of HHV-8 DNA in these cells that was associated with the detection of the latency-associated kaposin RNA. Finally, the addition of IFN-alpha reduced the HHV-8 load in PBMC. Thus, IFN-alpha appears to have inhibitory effects on HHV-8 persistent infection of PBMC. These results suggest that, in addition to inhibiting the expression of angiogenic factors that are key to KS development, IFN-alpha may induce KS regression by reducing the HHV-8 load and/or inhibiting virus reactivation.

Published
1999
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