95 results on '"Azab W"'
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2. Eco-friendly removal of methyl tert-butyl ether from contaminated water using steam and CO2-activated carbons.
- Author
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Bakry, M., El-Azab, W. I., El-Fiqi, A., and Ebiad, M. A.
- Subjects
BUTYL methyl ether ,WATER pollution ,PHYSISORPTION ,ADSORPTION kinetics ,WATER use ,GASOLINE - Abstract
Petrol frequently contains the additive methyl tertiary butyl ether (MTBE). Because of its significant health risks, MTBE pollution of surface and ground water is a severe concern for the environment. Highly porous physically activated carbons, particularly CO
2 -activated carbon (CO2 -AC) and steam-activated carbon (Steam-AC), were obtained from date stones as potential eco-friendly adsorbents for MTBE from contaminated water. The chemical composition, microstructure, textural, and structural characteristics of adsorbents were characterised by elemental analysis, SEM, N2 sorption, XRD, and FTIR. The adsorption process evaluation based on the initial MTBE concentration, liquid-to-solid ratio, and equilibrium contact time. CO2 -AC and steam-AC adsorbents have high surface areas of 819.5 m2 /g, and 567.7 m2 /g, respectively. At 40 °C, CO2 -AC has an adsorption capability of 181.36 mg/g. The adsorption result was best fitted by the Freundlich model. The two-step intraparticle diffusion process prevailed the adsorption process, and the pseudo-second-order model presented an optimal fit for the adsorption kinetics models. Spontaneous physical adsorption was endothermic when CO2 -AC adsorbs at 40 °C because ∆G was − 6.34 kJ/mol. Finally, the water quality improved and the salt content, the alkalinity, and the hardness decreased with the use of CO2 -AC as an environmentally friendly adsorbent for removing MTBE from the polluted water. [ABSTRACT FROM AUTHOR]- Published
- 2024
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3. Monitoring of elemental mercury in ambient air around an Egyptian natural gas processing plant
- Author
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El-Feky, A.A., El-Azab, W., Ebiad, M.A., Masod, Mohamed B., and Faramawy, S.
- Published
- 2018
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4. A hepatitis B virus causes chronic infections in equids worldwide
- Author
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Rasche A., Lehmann F., Goldmann N., Nagel M., Moreira-Soto A., Nobach D., de Oliveira Carneiro I., Osterrieder N., Greenwood A. D., Steinmann E., Lukashev A. N., Schuler G., Glebe D., Drexler J. F., Aguilar-Setien A., Azab W., Carluccio A., Dietrich D., Franke C. R., Garcia-Bocanegra I., Garcia-Lacy F., Jeworoski L. M., Jores J., Kepper R., Netto E. M., Owusu-Dabo E., Ribas J. R. L., Roncoroni C., Roppert P. L., Rusenov A., Rusenova N., Sandev N., Seeber P. A., Shnaiderman-Torban A., Steinman A., Tegtmeyer B., Veneziano V., Veronesi M. C., Walter S., Zapryanova D., Rasche, A., Lehmann, F., Goldmann, N., Nagel, M., Moreira-Soto, A., Nobach, D., de Oliveira Carneiro, I., Osterrieder, N., Greenwood, A. D., Steinmann, E., Lukashev, A. N., Schuler, G., Glebe, D., Drexler, J. F., Aguilar-Setien, A., Azab, W., Carluccio, A., Dietrich, D., Franke, C. R., Garcia-Bocanegra, I., Garcia-Lacy, F., Jeworoski, L. M., Jores, J., Kepper, R., Netto, E. M., Owusu-Dabo, E., Ribas, J. R. L., Roncoroni, C., Roppert, P. L., Rusenov, A., Rusenova, N., Sandev, N., Seeber, P. A., Shnaiderman-Torban, A., Steinman, A., Tegtmeyer, B., Veneziano, V., Veronesi, M. C., Walter, S., and Zapryanova, D.
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0301 basic medicine ,Drug Evaluation, Preclinical ,Hepacivirus ,Antibodies, Viral ,medicine.disease_cause ,0302 clinical medicine ,HBV ,Hepatocyte ,Cells, Cultured ,Multidisciplinary ,Coinfection ,virus diseases ,Hepatitis B viru ,Biological Sciences ,Hepatitis C ,Liver ,Female ,030211 gastroenterology & hepatology ,Antibody ,Viral load ,Human ,Hepatitis B virus ,Evolution ,Hepatitis C virus ,Primary Cell Culture ,Biology ,Antiviral Agents ,03 medical and health sciences ,Hepatitis B, Chronic ,Viral entry ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Animal model ,Antiviral Agent ,Hepaciviru ,Animal ,Horse ,Equidae ,Virus Internalization ,medicine.disease ,Virology ,digestive system diseases ,In vitro ,Disease Models, Animal ,030104 developmental biology ,Equid ,DNA, Viral ,Hepatocytes ,biology.protein - Abstract
Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by PCR and antibodies against EqHBV in 5.4% of donkeys and zebras. Molecular, histopathological, and biochemical analyses revealed that infection patterns of EqHBV resembled those of HBV in humans, including hepatotropism, moderate liver damage, evolutionary stasis, and potential horizontal virus transmission. Naturally infected donkeys showed chronic infections resembling CHB with high viral loads of up to 2.6 × 10(9) mean copies per milliliter serum for >6 mo and weak antibody responses. Antibodies against Equid HCV were codetected in 26.5% of donkeys seropositive for EqHBV, corroborating susceptibility to both hepatitis viruses. Deltavirus pseudotypes carrying EqHBV surface proteins were unable to infect human cells via the HBV receptor NTCP (Na(+)/taurocholate cotransporting polypeptide), suggesting alternative viral entry mechanisms. Both HBV and EqHBV deltavirus pseudotypes infected primary horse hepatocytes in vitro, supporting a broad host range for EqHBV among equids and suggesting that horses might be suitable for EqHBV and HBV infections in vivo. Evolutionary analyses suggested that EqHBV originated in Africa several thousand years ago, commensurate with the domestication of donkeys. In sum, EqHBV naturally infects diverse equids and mimics HBV infection patterns. Equids provide a unique opportunity for preclinical testing of novel therapeutics for CHB and to investigate HBV/HCV interplay upon coinfection.
- Published
- 2021
5. Synthesis and Characterization of some Alkyl Polyglycosides Surfactants
- Author
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El-Sukkary, M. M. A., Syed, Nagla A., Aiad, Ismail, and El-Azab, W. I. M.
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- 2008
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6. Crystal structure of glycoprotein D of Equine Herpesvirus Type 4
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Kremling, V., primary, Loll, B., additional, Osterrieder, N., additional, Wahl, M., additional, Dahmani, I., additional, Chiantia, P., additional, and Azab, W., additional
- Published
- 2020
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7. Crystal structure of glycoprotein D of Equine Herpesvirus Type 1
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Kremling, V., primary, Loll, B., additional, Azab, W., additional, Osterrieder, N., additional, Dahmani, I., additional, Chiantia, P., additional, and Wahl, M., additional
- Published
- 2020
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8. CULTIVATION OF GERBERA IRRIGATED WITH TREATED PETROLEUM REFINERY WASTEWATER
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Soliman E. M, El-azab W. I. M., and Ali N.
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Gerbera ,Fertigation ,Horticulture ,Irrigation ,biology ,Wastewater ,Loam ,Gerbera jamesonii ,Ornamental plant ,Floriculture ,Environmental science ,biology.organism_classification - Abstract
A detailed evaluation for the use of treated petroleum refinery wastewater in irrigation of Gerbera plants, vegetative growth, production and chemical compounds of Gerbera jamesonii were determined. The experiment was conducted for two successive seasons of 2014 and 2015 at the Floriculture Nursery under full sunlight conditions at Horticulture Research Institute, Ornamental Plants and Landscape Gardining Research Department, Egypt using clay loam soil and 30 cm pots. The mean plant height in harvest was 32.33 +1.86 and 25.67+ 2.18 cm for irrigation with treated wastewater at the first and second seasons respectively. Mean number of roots /plant in harvest was 42.33 +5.5 and 42.67+ 2.03 for irrigation with treated wastewater at the first and second seasons respectively. Mean flowers number / plant in harvest were 6.42 +1.1 and 6.81+ 1.3 for irrigation with treated wastewater at the first and second seasons respectively. Mean flower diameters in harvest were 7.44 +1.14 and 7.1+ 1.18 cm for irrigation with treated wastewater at the first and second seasons respectively. The mean numbers of leaves / plant in harvest were 8.33 +0.37 and 6.0+ 1.0 for irrigation with treated wastewater at the first and second seasons respectively.
- Published
- 2017
9. Fatal Elephant Endotheliotropic Herpesvirus Infection of Two Young Asian Elephants
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Pavulraj, S, Eschke, K, Prahl, A, Flugger, M, Trimpert, J, van den Doel, Petra, Andreotti, S, Kaessmeyer, S, Osterrieder, N, Azab, W, Pavulraj, S, Eschke, K, Prahl, A, Flugger, M, Trimpert, J, van den Doel, Petra, Andreotti, S, Kaessmeyer, S, Osterrieder, N, and Azab, W
- Published
- 2019
10. Load management strategies for redundant equipment in smart grids
- Author
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Samoylenko, V. V., primary, Samoylenko, I. V., additional, Fedorenko, V. V., additional, and Azab, W. S., additional
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- 2018
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11. Size-dependent inhibition of herpesvirus cellular entry by polyvalent nanoarchitectures
- Author
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Ziem, B., primary, Azab, W., additional, Gholami, M. F., additional, Rabe, J. P., additional, Osterrieder, N., additional, and Haag, R., additional
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- 2017
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12. Evaluation of immunity and clinical disease following infection of horses with Equine herpesvirus-1 and mutants of differing neuropathogenic potential
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Holz, C.L., primary, Wilson, M.E., additional, Zarski, L., additional, Nelli, R.K., additional, Pease, A., additional, Azab, W., additional, Osterrieder, N., additional, Goehring, L.S., additional, Sledge, D., additional, Kiupel, M., additional, and Soboll Hussey, G., additional
- Published
- 2016
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13. The Biosorption of Phenol from Petroleum Refinery Wastewater Using Spent Waste Biomass
- Author
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Younis, Sh. A., primary, El-Gendy, N. Sh., additional, El-Azab, W. I., additional, Moustafa, Y. M., additional, and Hashem, A. I., additional
- Published
- 2014
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14. Third International Havemeyer Workshop on Equine Herpesvirus type 1
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Kydd, J. H., primary, Slater, J., additional, Osterrieder, N., additional, Lunn, D. P., additional, Antczak, D. F., additional, Azab, W., additional, Balasuriya, U., additional, Barnett, C., additional, Brosnahan, M., additional, Cook, C., additional, Damiani, A., additional, Elton, D., additional, Frampton, A., additional, Gilkerson, J., additional, Goehring, L., additional, Horohov, D., additional, Maxwell, L., additional, Minke, J., additional, Morley, P., additional, Nauwynck, H., additional, Newton, R., additional, Perkins, G., additional, Pusterla, N., additional, Soboll‐Hussey, G., additional, Traub‐Dargatz, J., additional, Townsend, H., additional, Van de walle, G. R., additional, and Wagner, B., additional
- Published
- 2012
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15. Molecular, Surface, and Thermodynamic Properties of Nonionic Surfactants Based on Castor Oil
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El-Azab, W. I. M., primary, Aiad, I., additional, Azzam, E. M. S., additional, and Gad, E. A. M., additional
- Published
- 2010
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16. Fragmentation Mechanism of Alkyl-monoglycosides by Mass Spectrometry
- Author
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Sayed, N. A., primary, Sukkary, M. EL, additional, Aiad, A., additional, and El-Azab, W., additional
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- 2010
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17. Aqueous Solution Properties, Biodegradability, and Antimicrobial Activity of some Alkylpolyglycosides Surfactants
- Author
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El-Sukkary, M. M. A., primary, Syed, N. A., additional, Aiad, Ismail, additional, Helmy, S. M., additional, and El-Azab, W. I. M., additional
- Published
- 2009
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18. Molecular, Surface, Thermodynamic Properties and Biodegradability of Nonionic Surfactants Based on Castor Oil
- Author
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Gad, E. A. M., primary, Azzam, E. M. S., additional, Aiad, I., additional, and El-azab, W. I. M., additional
- Published
- 2009
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19. The role of glycoprotein H of equine herpesviruses 1 and 4 (EHV-1 and EHV-4) in cellular host range and integrin binding
- Author
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Azab Walid, Zajic Lara, and Osterrieder Nikolaus
- Subjects
Veterinary medicine ,SF600-1100 - Abstract
Abstract Equine herpesvirus type 1 and 4 (EHV-1 and EHV-4) glycoprotein H (gH) has been hypothesized to play a role in direct fusion of the virus envelope with cellular membranes. To investigate gH’s role in infection, an EHV-1 mutant lacking gH was created and the gH genes were exchanged between EHV-1 and EHV-4 to determine if gH affects cellular entry and/or host range. In addition, a serine-aspartic acid-isoleucine (SDI) integrin-binding motif present in EHV-1 gH was mutated as it was presumed important in cell entry mediated by binding to α4β1 or α4β7 integrins. We here document that gH is essential for EHV-1 replication, plays a role in cell-to-cell spread and significantly affects plaque size and growth kinetics. Moreover, we could show that α4β1 and α4β7 integrins are not essential for viral entry of EHV-1 and EHV-4, and that viral entry is not affected in equine cells when the integrins are inaccessible.
- Published
- 2012
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20. Persisting embryonal infundibular recess (PEIR) and transsphenoidal-transsellar encephaloceles: distinct entities or constituents of one continuum?
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Waleed A. Azab, Luigi Maria Cavallo, Waleed Yousef, Tufail Khan, Domenico Solari, Paolo Cappabianca, Azab, W. A., Cavallo, L. M., Yousef, W., Khan, T., Solari, D., and Cappabianca, P.
- Subjects
Endoscopic ,Transsphenoidal transsellar encephalocele ,Pituitary Gland ,Pediatrics, Perinatology and Child Health ,Humans ,Persisting embryonal infundibular recess (PEIR) ,Neurology (clinical) ,General Medicine ,Human ,Encephalocele ,Third Ventricle - Abstract
Persisting embryonal infundibular recess (PEIR) is a very rare anomaly of the floor of the third ventricle in which the embryonic morphology of the infundibular recess (IR) persists. The exact underlying mechanism of development of PEIR is unknown, and the anomaly has been reported as an isolated finding or in association with other conditions. On the other hand, trans-sphenoidal encephaloceles are the rarest form of basal encephaloceles. The trans-sphenoidal trans-sellar encephalocele (TSE) is the least common variant in which the pituitary gland, pituitary stalk, optic pathways, parts of the third ventricle and IR may be present within the encephalocele. We recently treated one patient with TSE. Based on the observed morphological similarity of the IR in our patient and in the published cases of PEIR, we reviewed the literature in order to validate the hypothesis that PEIR and TSE may possibly belong to one spectrum of malformations. Across the published reports, the morphology of the IR in TSE is very closely similar to PEIR. Moreover, radiological, patho-anatomical, and embryological evidence is in support to our hypothesis that PEIR and TSE are most likely the two extremes of the same continuum of malformations.
- Published
- 2022
21. Pituitary Adenomas
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Paolo Cappabianca, Chiara Caggiano, Domenico Solari, Karol Migliorati, Waleed A. Azab, Elia Guadagno, Marialaura Del Basso De Caro, Emmanuel Jouanneau, Luigi M. Cavallo, Cappabianca, P., Caggiano, C., Solari, D., Migliorati, K., Azab, W. A., Guadagno, E., De Caro, M. D. B., Jouanneau, E., and Cavallo, L. M.
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Elderly ,Endoscopic endonasal transsphenoidal approach ,Pituitary adenomas - Abstract
Because of the increasing life expectancy and improving of diagnostic methods, management of pituitary adenomas in elderly patients is growing with time and, actually, the incidence rate has reached value of 7-10 %; more than 80 % of these lesions result in non-functioning pituitary adenomas. Visual field defects and hypopituitarism, both related to mass effect, remain the leading symptoms, although these masses can be completely asymptomatic (pituitary incidentalomas) or eventually disclosed upon occurrence of apoplexy (10 %). Nevertheless, because ageing is related to several endocrinological and metabolic changes, including significant modification of the hypothalamo-hypophyseal functions, clinical features of the eventual pituitary disorder may be misdiagnosed. The rates of prevalence for macroadenomas in elderly are higher as compared to the other age groups, but these tumours do not present inner increased invasiveness, probably due to the lower cell proliferation rate identified. The surgical management of pituitary adenomas in the elderly is somehow burdened by the presence of mild and/or severe systemic co-morbidities (specially cardiovascular, respiratory and neurological disorders) found in more than 50 % of patients; this aspect dramatically increases anaesthesiological risk and significantly the mortality rate between young and elderly patients. Endoscopic endonasal approach is usually safe and successful in this group of patients, and the ophthalmological and endocrinological outcomes are satisfactory as those of the younger group, also at a long follow-up.
- Published
- 2017
22. Endoscopic trans-septal interforniceal approach for excision of colloid cysts of the third ventricle using the rotational technique.
- Author
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Saleem A, Najibullah M, Shabbir Z, and Azab W
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- Child, Humans, Endoscopy methods, Neurosurgical Procedures methods, Brain Neoplasms surgery, Colloid Cysts diagnostic imaging, Colloid Cysts surgery, Colloid Cysts pathology, Third Ventricle diagnostic imaging, Third Ventricle surgery, Third Ventricle pathology
- Abstract
Colloid cysts of the third ventricle are benign intracranial lesions that account for 0.5 to 2% of all brain tumors and are even rarer in pediatric population. Dandy was the first to successfully excise a colloid cyst of the third ventricle via a transcortical transventricular approach in 1921. For several decades to follow, the transcortical transventricular and transcallosal microsurgical approaches remained the cornerstone of surgical management of these lesions. With time and refinements in endoscopic equipment and techniques, endoscopic resection of colloid cysts evolved into a currently well-established and appealing minimally invasive alternative to microsurgery. Endoscopic endochannel techniques for colloid cysts of the third ventricle may either be transforaminal or trans-septal interforniceal, depending on the pathoanatomical features of the colloid cyst and its relation to the juxtaposed anatomical structures. The endoscopic trans-septal interforniceal approach is required to access the rare subset of colloid cysts that extend superior to the roof of the third ventricle between the two fornices insinuating themselves between the leaflets of the septum pellucidum. In this article, the surgical technique of the endochannel endoscopic trans-septal interforniceal approach is elaborated upon. A representative case is presented along with an operative video., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2023
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23. Editorial: Herpesviruses of animals: recent advances and updates.
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Pavulraj S and Azab W
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
- Published
- 2023
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24. Crystal structures of glycoprotein D of equine alphaherpesviruses reveal potential binding sites to the entry receptor MHC-I.
- Author
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Kremling V, Loll B, Pach S, Dahmani I, Weise C, Wolber G, Chiantia S, Wahl MC, Osterrieder N, and Azab W
- Abstract
Cell entry of most alphaherpesviruses is mediated by the binding of glycoprotein D (gD) to different cell surface receptors. Equine herpesvirus type 1 (EHV-1) and EHV-4 gDs interact with equine major histocompatibility complex I (MHC-I) to initiate entry into equine cells. We have characterized the gD-MHC-I interaction by solving the crystal structures of EHV-1 and EHV-4 gDs (gD1, gD4), performing protein-protein docking simulations, surface plasmon resonance (SPR) analysis, and biological assays. The structures of gD1 and gD4 revealed the existence of a common V-set immunoglobulin-like (IgV-like) core comparable to those of other gD homologs. Molecular modeling yielded plausible binding hypotheses and identified key residues (F213 and D261) that are important for virus binding. Altering the key residues resulted in impaired virus growth in cells, which highlights the important role of these residues in the gD-MHC-I interaction. Taken together, our results add to our understanding of the initial herpesvirus-cell interactions and will contribute to the targeted design of antiviral drugs and vaccine development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kremling, Loll, Pach, Dahmani, Weise, Wolber, Chiantia, Wahl, Osterrieder and Azab.)
- Published
- 2023
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25. Endoscope-controlled extended supraorbital keyhole approach through a modified eyebrow incision for a large dural-based solitary fibrous tumor of the frontal convexity: A technical note.
- Author
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Azab W, Najibullah M, and Waheed G
- Abstract
Background: The extended supraorbital approach through a modified eyebrow incision is a minimally invasive approach that has been recently described. It entails a lateral extension of the skin incision beyond the lateral end of the eyebrow and allows exposure of the proximal sylvian fissure with a superior degree of surgical freedom in the middle fossa and the parasellar region. In this technical note, we describe an endoscope-controlled extended supraorbital keyhole approach with modified eyebrow incision for excision of a large dural-based solitary fibrous tumor of the left frontal convexity., Methods: An endoscope-controlled extended supraorbital keyhole approach with modified eyebrow incision was performed to excise a large extra-axial mass attached to the dura of the left frontal convexity and extends from the superior temporal line up to the midline in a 34-year-old male patient presented with 1-year history of headache, dizziness, and blurred vision., Results: The patient had an uneventful postoperative course with gross total excision of the lesion and satisfying cosmetic appearance. Histopathological examination revealed a Grade 1 solitary fibrous tumor., Conclusion: We demonstrated the feasibility of the endoscope-controlled extended supraorbital keyhole approach through a modified eyebrow incision for excision of tumors that abut the inner table of the frontal calvarial bone, extend highly above the skull base level, or extend medially reaching the midline. The approach is very versatile and allows a great exposure for a category of lesions deemed not perfectly suitable for the classic supraorbital keyhole approach., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)
- Published
- 2022
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26. The US3 Kinase of Herpes Simplex Virus Phosphorylates the RNA Sensor RIG-I To Suppress Innate Immunity.
- Author
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van Gent M, Chiang JJ, Muppala S, Chiang C, Azab W, Kattenhorn L, Knipe DM, Osterrieder N, and Gack MU
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- Alphaherpesvirinae genetics, Alphaherpesvirinae metabolism, Alphaherpesvirinae physiology, Amino Acid Sequence, DEAD Box Protein 58 chemistry, HEK293 Cells, Herpesvirus 1, Human genetics, Herpesvirus 1, Human metabolism, Humans, Immunity, Innate, Interferon Type I metabolism, Phosphorylation, Protein Binding, Protein Serine-Threonine Kinases genetics, Receptors, Immunologic chemistry, Viral Proteins genetics, DEAD Box Protein 58 metabolism, Herpesvirus 1, Human immunology, Immune Evasion, Protein Serine-Threonine Kinases metabolism, Receptors, Immunologic metabolism, Viral Proteins metabolism
- Abstract
Recent studies have demonstrated that the signaling activity of the cytosolic pathogen sensor retinoic acid-inducible gene-I (RIG-I) is modulated by a variety of posttranslational modifications (PTMs) to fine-tune the antiviral type I interferon (IFN) response. Whereas K63-linked ubiquitination of the RIG-I caspase activation and recruitment domains (CARDs) catalyzed by TRIM25 or other E3 ligases activates RIG-I, phosphorylation of RIG-I at S8 and T170 represses RIG-I signal transduction by preventing the TRIM25-RIG-I interaction and subsequent RIG-I ubiquitination. While strategies to suppress RIG-I signaling by interfering with its K63-polyubiquitin-dependent activation have been identified for several viruses, evasion mechanisms that directly promote RIG-I phosphorylation to escape antiviral immunity are unknown. Here, we show that the serine/threonine (Ser/Thr) kinase US3 of herpes simplex virus 1 (HSV-1) binds to RIG-I and phosphorylates RIG-I specifically at S8. US3-mediated phosphorylation suppressed TRIM25-mediated RIG-I ubiquitination, RIG-I-MAVS binding, and type I IFN induction. We constructed a mutant HSV-1 encoding a catalytically-inactive US3 protein (K220A) and found that, in contrast to the parental virus, the US3 mutant HSV-1 was unable to phosphorylate RIG-I at S8 and elicited higher levels of type I IFNs, IFN-stimulated genes (ISGs), and proinflammatory cytokines in a RIG-I-dependent manner. Finally, we show that this RIG-I evasion mechanism is conserved among the alphaherpesvirus US3 kinase family. Collectively, our study reveals a novel immune evasion mechanism of herpesviruses in which their US3 kinases phosphorylate the sensor RIG-I to keep it in the signaling-repressed state. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes lifelong latency in the majority of the human population worldwide. HSV-1 occasionally reactivates to produce infectious virus and to facilitate dissemination. While often remaining subclinical, both primary infection and reactivation occasionally cause debilitating eye diseases, which can lead to blindness, as well as life-threatening encephalitis and newborn infections. To identify new therapeutic targets for HSV-1-induced diseases, it is important to understand the HSV-1-host interactions that may influence infection outcome and disease. Our work uncovered direct phosphorylation of the pathogen sensor RIG-I by alphaherpesvirus-encoded kinases as a novel viral immune escape strategy and also underscores the importance of RNA sensors in surveilling DNA virus infection.
- Published
- 2022
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27. Contamination Control Strategy: Implementation Road Map.
- Author
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El Azab W
- Subjects
- Drug Contamination prevention & control
- Abstract
The article proposes an implementation road map of a contamination control strategy (CCS) in a facility. The CCS is the culmination of an exercise to identify activities designed to prevent microorganism, pyrogen, and particulate contamination in the product, the facility, and the supporting processes used to manufacture the product. Manufacturers can formulate their contamination control strategy based on information in the quality target product profile or in the critical quality attributes, in the facility, and in the processes used to manufacture and transport the product. The strategy implementation involves executing the strategic plan and managing the implementation by priority overtime should it be deployed. The evaluation of the efficiency and effectiveness of the contamination control strategy implemented is confirmed by analyzing and trending the various quality performance parameters related to contamination control. The strategy evaluation allows the manufacturer to identify a new strategic plan to support improvement goals or new measures and/or controls to achieve the desired result, minimizing the contamination risk., (© PDA, Inc. 2021.)
- Published
- 2021
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28. Equine Herpesvirus Type 4 (EHV-4) Outbreak in Germany: Virological, Serological, and Molecular Investigations.
- Author
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Pavulraj S, Eschke K, Theisen J, Westhoff S, Reimers G, Andreotti S, Osterrieder N, and Azab W
- Abstract
Equine herpesvirus type 4 (EHV-4) is enzootic in equine populations throughout the world. A large outbreak of EHV-4 respiratory infection occurred at a Standardbred horse-breeding farm in northern Germany in 2017. Respiratory illness was observed in a group of in-housed foals and mares, which subsequently resulted in disease outbreak. Out of 84 horses in the stud, 76 were tested and 41 horses were affected, including 20 foals, 10 stallions, and 11 mares. Virological investigations revealed the involvement of EHV-4 in all cases of respiratory illness, as confirmed by virus isolation, qPCR, and/or serological follow-up using virus neutralization test and peptide-specific ELISA. Among infected mares, 73% (8 out of 11) and their corresponding foals shed the virus at the same time. EHV-4 was successfully isolated from four animals (including one stallion and three foals), and molecular studies revealed a different restriction fragment length polymorphism (RFLP) profile in all four isolates. We determined the complete 144 kbp genome sequence of EHV-4 isolated from infected horses by next-generation sequencing and de novo assembly. Hence, EHV-4 is genetically stable in nature, different RFLP profiles, and genome sequences of the isolates, suggesting the involvement of more than one animal as a source of infection due to either true infection or reactivation from a latent state. In addition, epidemiological investigation revealed that stress caused by seasonal changes, management practices, routine equestrian activities, and exercises contributed as a multifactorial causation for disease outbreak. This study shows the importance of implementing stress alleviating measures and management practices in breeding farms in order to avoid immunosuppression and occurrence of disease.
- Published
- 2021
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29. Seasonal host and ecological drivers may promote restricted water as a viral vector.
- Author
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Dayaram A, Seeber P, Courtiol A, Soilemetzidou S, Tsangaras K, Franz M, McEwen GK, Azab W, Kaczensky P, Melzheimer J, East ML, Ganbaatar O, Walzer C, Osterrieder N, and Greenwood AD
- Subjects
- Animals, Phylogeny, Seasons, Water, Herpesviridae, Herpesviridae Infections
- Abstract
In climates with seasonally limited precipitation, terrestrial animals congregate at high densities at scarce water sources. We hypothesize that viruses can exploit the recurrence of these diverse animal congregations to spread. In this study, we test the central prediction of this hypothesis - that viruses employing this transmission strategy remain stable and infectious in water. Equid herpesviruses (EHVs) were chosen as a model as they have been shown to remain stable and infectious in water for weeks under laboratory conditions. Using fecal data from wild equids from a previous study, we establish that EHVs are shed more frequently by their hosts during the dry season, increasing the probability of water source contamination with EHV. We document the presence of several strains of EHVs present in high genome copy number from the surface water and sediments of waterholes sampled across a variety of mammalian assemblages, locations, temperatures and pH. Phylogenetic analysis reveals that the different EHV strains found exhibit little divergence despite representing ancient lineages. We employed molecular approaches to show that EHVs shed remain stable in waterholes with detection decreasing with increasing temperature in sediments. Infectivity experiments using cell culture reveals that EHVs remain infectious in water derived from waterholes. The results are supportive of water as an abiotic viral vector for EHV., Competing Interests: Declaration of competing interest We declare that all the authors have no competing financial interests in relation to the work described., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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30. Graphene-Assisted Synthesis of 2D Polyglycerols as Innovative Platforms for Multivalent Virus Interactions.
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Mohammadifar E, Ahmadi V, Gholami MF, Oehrl A, Kolyvushko O, Nie C, Donskyi IS, Herziger S, Radnik J, Ludwig K, Böttcher C, Rabe JP, Osterrieder K, Azab W, Haag R, and Adeli M
- Abstract
2D nanomaterials have garnered widespread attention in biomedicine and bioengineering due to their unique physicochemical properties. However, poor functionality, low solubility, intrinsic toxicity, and nonspecific interactions at biointerfaces have hampered their application in vivo. Here, biocompatible polyglycerol units are crosslinked in two dimensions using a graphene-assisted strategy leading to highly functional and water-soluble polyglycerols nanosheets with 263 ± 53 nm and 2.7 ± 0.2 nm average lateral size and thickness, respectively. A single-layer hyperbranched polyglycerol containing azide functional groups is covalently conjugated to the surface of a functional graphene template through pH-sensitive linkers. Then, lateral crosslinking of polyglycerol units is carried out by loading tripropargylamine on the surface of graphene followed by lifting off this reagent for an on-face click reaction. Subsequently, the polyglycerol nanosheets are detached from the surface of graphene by slight acidification and centrifugation and is sulfated to mimic heparin sulfate proteoglycans. To highlight the impact of the two-dimensionality of the synthesized polyglycerol sulfate nanosheets at nanobiointerfaces, their efficiency with respect to herpes simplex virus type 1 and severe acute respiratory syndrome corona virus 2 inhibition is compared to their 3D nanogel analogs. Four times stronger in virus inhibition suggests that 2D polyglycerols are superior to their current 3D counterparts., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Functional Materials published by Wiley‐VCH GmbH.)
- Published
- 2021
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31. Immunogenicity of Calvenza-03 EIV/EHV ® Vaccine in Horses: Comparative In Vivo Study.
- Author
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Pavulraj S, Bergmann T, Trombetta CM, Marchi S, Montomoli E, Alami SSE, Ragni-Alunni R, Osterrieder N, and Azab W
- Abstract
Equine influenza (EI) is a highly contagious acute respiratory disease of equines that is caused mainly by the H3N8 subtype of influenza A virus. Vaccinating horses against EI is the most effective strategy to prevent the infection. The current study aimed to compare the kinetics of EI-specific humoral- and cell-mediated immunity (CMI) in horses receiving either identical or mixed vaccinations. Two groups of horses were previously (six months prior) vaccinated with either Calvenza 03 EIV EHV
® (G1) or Fluvac Innovator® (G2) vaccine. Subsequently, both groups received a booster single dose of Calvenza 03 EIV EHV® . Immune responses were assessed after 10 weeks using single radial hemolysis (SRH), virus neutralization (VN), and EliSpot assays. Our results revealed that Calvenza-03 EIV/EHV® -immunized horses had significantly higher protective EI-specific SRH antibodies and VN antibodies. Booster immunization with Calvenza-03 EIV/EHV® vaccine significantly stimulated cell-mediated immune response as evidenced by significant increase in interferon-γ-secreting peripheral blood mononuclear cells. In conclusion, Calvenza-03 EIV/EHV® vaccine can be safely and effectively used for booster immunization to elicit optimal long persisting humoral and CMI responses even if the horses were previously immunized with a heterogeneous vaccine.- Published
- 2021
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32. Equid Herpesvirus-1 Exploits the Extracellular Matrix of Mononuclear Cells to Ensure Transport to Target Cells.
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Kamel M, Pavulraj S, Fauler B, Mielke T, and Azab W
- Abstract
Mononuclear cells are the first line of defense against microbial infection. Yet, several viruses have evolved different mechanisms to overcome host defenses to ensure their spread. Here, we show unique mechanisms of how equid herpesvirus-1 manipulates peripheral blood mononuclear cells (PBMC) to travel further in the body. (1) "PBMC-hitching": at the initial contact, herpesviruses lurk in the extracellular matrix (ECM) of PBMC without entering the cells. The virus exploits the components of the ECM to bind, transport, and then egress to infect other cells. (2) "Intracellular delivery": transendothelial migration is a physiological mechanism where mononuclear cells can transmigrate through the endothelial cells. The virus was intangible and probably did not interfere with such a mechanism where the infected PBMC can probably deliver the virus inside the endothelium. (3) "Classical-fusion": this process is well mastered by herpesviruses due to a set of envelope glycoproteins that facilitate cell-cell fusion and virus spread., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)
- Published
- 2020
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33. Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs.
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Pavulraj S, Kamel M, Stephanowitz H, Liu F, Plendl J, Osterrieder N, and Azab W
- Subjects
- Animals, Chemokines genetics, Cytokines genetics, Herpesviridae Infections genetics, Herpesviridae Infections immunology, Herpesviridae Infections virology, Herpesvirus 1, Equid genetics, Horse Diseases genetics, Horse Diseases virology, Horses, Host-Pathogen Interactions, Leukocytes, Mononuclear immunology, Virus Replication, Chemokines immunology, Cytokines immunology, Herpesviridae Infections veterinary, Herpesvirus 1, Equid physiology, Horse Diseases immunology, Leukocytes, Mononuclear virology
- Abstract
Equine herpesvirus type 1 (EHV-1) causes encephalomyelopathy and abortion, for which cell-associated viremia and subsequent virus transfer to and replication in endothelial cells (EC) are responsible and prerequisites. Viral and cellular molecules responsible for efficient cell-to-cell spread of EHV-1 between peripheral blood mononuclear cells (PBMC) and EC remain unclear. We have generated EHV-1 mutants lacking ORF1 , ORF2 , and ORF17 genes, either individually or in combination. Mutant viruses were analyzed for their replication properties in cultured equine dermal cells, PBMC infection efficiency, virus-induced changes in the PBMC proteome, and cytokine and chemokine expression profiles. ORF1 , ORF2 , and ORF17 are not essential for virus replication, but ORF17 deletion resulted in a significant reduction in plaque size. Deletion of ORF2 and ORF17 gene significantly reduced cell-to-cell virus transfer from virus-infected PBMC to EC. EHV-1 infection of PBMC resulted in upregulation of several pathways such as Ras signaling, oxidative phosphorylation, platelet activation and leukocyte transendothelial migration. In contrast, chemokine signaling, RNA degradation and apoptotic pathways were downregulated. Deletion of ORF1 , ORF2 and ORF17 modulated chemokine signaling and MAPK pathways in infected PBMC, which may explain the impairment of virus spread between PBMC and EC. The proteomic results were further confirmed by chemokine assays, which showed that virus infection dramatically reduced the cytokine/chemokine release in infected PBMC. This study uncovers cellular proteins and pathways influenced by EHV-1 after PBMC infection and provide an important resource for EHV-1 pathogenesis. EHV-1-immunomodulatory genes could be potential targets for the development of live attenuated vaccines or therapeutics against virus infection., Competing Interests: The authors declare no conflict of interest.
- Published
- 2020
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34. Equine Alphaherpesviruses Require Activation of the Small GTPases Rac1 and Cdc42 for Intracellular Transport.
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Kolyvushko O, Kelch MA, Osterrieder N, and Azab W
- Abstract
Viruses utilize host cell signaling to facilitate productive infection. Equine herpesvirus type 1 (EHV-1) has been shown to activate Ca2+ release and phospholipase C upon contact with α4β1 integrins on the cell surface. Signaling molecules, including small GTPases, have been shown to be activated downstream of Ca2+ release, and modulate virus entry, membrane remodeling and intracellular transport. In this study, we show that EHV-1 activates the small GTPases Rac1 and Cdc42 during infection. The activation of Rac1 and Cdc42 is necessary for virus-induced acetylation of tubulin, effective viral transport to the nucleus, and cell-to-cell spread. We also show that inhibitors of Rac1 and Cdc42 did not block virus entry, but inhibited overall virus infection. The Rac1 and Cdc42 signaling is presumably orthogonal to Ca2+ release, since Rac1 and Cdc42 inhibitors affected the infection of both EHV-1 and EHV-4, which do not bind to integrins.
- Published
- 2020
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35. Macropinocytosis and Clathrin-Dependent Endocytosis Play Pivotal Roles for the Infectious Entry of Puumala Virus.
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Bauherr S, Larsberg F, Petrich A, Sperber HS, Klose-Grzelka V, Luckner M, Azab W, Schade M, Höfer CT, Lehmann MJ, Witkowski PT, Krüger DH, Herrmann A, and Schwarzer R
- Subjects
- Animals, Chlorocebus aethiops, Hemorrhagic Fever with Renal Syndrome pathology, Vero Cells, Clathrin metabolism, Hemorrhagic Fever with Renal Syndrome metabolism, Pinocytosis, Puumala virus metabolism, Virus Internalization
- Abstract
Viruses from the family Hantaviridae are encountered as emerging pathogens causing two life-threatening human zoonoses: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), with case fatality rates of up to 50%. Here, we comprehensively investigated entry of the Old World hantavirus Puumala virus (PUUV) into mammalian cells, showing that upon treatment with pharmacological inhibitors of macropinocytosis and clathrin-mediated endocytosis, PUUV infections are greatly reduced. We demonstrate that the inhibitors did not interfere with viral replication and that RNA interference, targeting cellular mediators of macropinocytosis, decreases PUUV infection levels significantly. Moreover, we established lipophilic tracer staining of PUUV particles and show colocalization of stained virions and markers of macropinosomes. Finally, we report a significant increase in the fluid-phase uptake of cells infected with PUUV, indicative of a virus-triggered promotion of macropinocytosis. IMPORTANCE The family Hantaviridae comprises a diverse group of virus species and is considered an emerging global public health threat. Individual hantavirus species differ considerably in terms of their pathogenicity but also in their cell biology and host-pathogen interactions. In this study, we focused on the most prevalent pathogenic hantavirus in Europe, Puumala virus (PUUV), and investigated the entry and internalization of PUUV into mammalian cells. We show that both clathrin-mediated endocytosis and macropinocytosis are cellular pathways exploited by the virus to establish productive infections and demonstrate that pharmacological inhibition of macropinocytosis or a targeted knockdown using RNA interference significantly reduced viral infections. We also found indications of an increase of macropinocytic uptake upon PUUV infection, suggesting that the virus triggers specific cellular mechanisms in order to stimulate its own internalization, thus facilitating infection., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2020
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36. Differentially-Charged Liposomes Interact with Alphaherpesviruses and Interfere with Virus Entry.
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Kolyvushko O, Latzke J, Dahmani I, Osterrieder N, Chiantia S, and Azab W
- Abstract
Exposure of phosphatidylserine (PS) in the outer leaflet of the plasma membrane is induced by infection with several members of the Alphaherpesvirinae subfamily. There is evidence that PS is used by the equine herpesvirus type 1 (EHV-1) during entry, but the exact role of PS and other phospholipids in the entry process remains unknown. Here, we investigated the interaction of differently charged phospholipids with virus particles and determined their influence on infection. Our data show that liposomes containing negatively charged PS or positively charged DOTAP (N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium) inhibited EHV-1 infection, while neutral phosphatidylcholine (PC) had no effect. Inhibition of infection with PS was transient, decreased with time, and was dose dependent. Our findings indicate that both cationic and anionic phospholipids can interact with the virus and reduce infectivity, while, presumably, acting through different mechanisms. Charged phospholipids were found to have antiviral effects and may be used to inhibit EHV-1 infection.
- Published
- 2020
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37. Bearing the brunt: Mongolian khulan (Equus hemionus hemionus) are exposed to multiple influenza A strains.
- Author
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Soilemetzidou ES, de Bruin E, Eschke K, Azab W, Osterrieder N, Czirják GÁ, Buuveibaatar B, Kaczensky P, Koopmans M, Walzer C, and Greenwood AD
- Subjects
- Animals, Animals, Wild virology, Antibodies, Viral blood, Disease Reservoirs virology, Ecosystem, Influenza A Virus, H3N8 Subtype pathogenicity, Influenza A Virus, H7N7 Subtype pathogenicity, Influenza A virus classification, Influenza A virus pathogenicity, Mongolia epidemiology, Orthomyxoviridae Infections epidemiology, Orthomyxoviridae Infections virology, Disease Reservoirs veterinary, Equidae virology, Influenza A virus immunology, Orthomyxoviridae Infections transmission
- Abstract
The majority of influenza A virus strains are hosted in nature by avian species in the orders of Anseriformes and Charadriformes. A minority of strains have been able to cross species boundaries and establish themselves in novel non-avian hosts. Influenza viruses of horses, donkeys, and mules represent such successful events of avian to mammal influenza virus adaptation. Mongolia has over 3 million domestic horses and is home to two wild equids, the Asiatic wild ass or khulan (Equus hemionus hemionus), and Przewalski's horse (Equus ferus przewalskii). Domestic and wild equids are sympatric across most of their range in Mongolia. Epizootic influenza A virus outbreaks among Mongolian domestic horses have been frequently recorded. However, the exposure, circulation and relation to domestic horse influenza A virus outbreaks among wild equids is unknown. We evaluated serum samples of Asiatic wild asses in Mongolia for antibodies against influenza A viruses, using modified protein microarray technique. We detected antibodies against hemagglutinin (H) H1, H3, H5, H7, H8 and H10 influenza A viruses. Asiatic wild asses may represent a previously unidentified influenza A virus reservoir in an ecosystem shared with populations of domestic horses in which influenza strains circulate., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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38. Fatal Elephant Endotheliotropic Herpesvirus Infection of Two Young Asian Elephants.
- Author
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Pavulraj S, Eschke K, Prahl A, Flügger M, Trimpert J, van den Doel PB, Andreotti S, Kaessmeyer S, Osterrieder N, and Azab W
- Abstract
Elephant endotheliotropic herpesvirus (EEHV) can cause a devastating haemorrhagic disease in young Asian elephants worldwide. Here, we report the death of two young Asian elephants after suffering from acute haemorrhagic disease due to EEHV-1A infection. We detected widespread distribution of EEHV-1A in various organs and tissues of the infected elephants. Enveloped viral particles accumulated within and around cytoplasmic electron-dense bodies in hepatic endothelial cells were detected. Attempts to isolate the virus on different cell cultures showed limited virus replication; however, late viral protein expression was detected in infected cells. We further showed that glycoprotein B (gB) of EEHV-1A possesses a conserved cleavage site Arg-X-Lys/Arg-Arg that is targeted by the cellular protease furin, similar to other members of the Herpesviridae . We have determined the complete 180 kb genome sequence of EEHV-1A isolated from the liver by next-generation sequencing and de novo assembly. As virus isolation in vitro has been unsuccessful and limited information is available regarding the function of viral proteins, we have attempted to take the initial steps in the development of suitable cell culture system and virus characterization. In addition, the complete genome sequence of an EEHV-1A in Europe will facilitate future studies on the epidemiology and diagnosis of EEHV infection in elephants.
- Published
- 2019
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39. Functionalized nanographene sheets with high antiviral activity through synergistic electrostatic and hydrophobic interactions.
- Author
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Donskyi IS, Azab W, Cuellar-Camacho JL, Guday G, Lippitz A, Unger WES, Osterrieder K, Adeli M, and Haag R
- Abstract
As resistance to traditional drugs emerges for treatment of virus infections, the need for new methods for virus inhibition increases. Graphene derivatives with large surface areas have shown strong activity against different viruses. However, the inability of current synthetic protocols to accurately manipulate the structure of graphene sheets in order to control their antiviral activity remains a major challenge. In this work, a series of graphene derivatives with defined polyglycerol sulfate and fatty amine functionalities have been synthesized and their interactions with herpes simplex virus type 1 (HSV-1) are investigated. While electrostatic interactions between polyglycerol sulfate and virus particles trigger the binding of graphene to virus, alkyl chains induce a high antiviral activity by secondary hydrophobic interactions. Among graphene sheets with a broad range of alkyl chains, (C3-C18), the C12-functionalized sheets showed the highest antiviral activity, indicating the optimum synergistic effect between electrostatic and hydrophobic interactions, but this derivative was toxic against the Vero cell line. In contrast, sheets functionalized with C6- and C9-alkyl chains showed low toxicity against Vero cells and a synergistic inhibition of HSV-1. This study shows that antiviral agents against HSV-1 can be obtained by controlled and stepwise functionalization of graphene sheets and may be developed into antiviral agents for future biomedical applications.
- Published
- 2019
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40. Detection of equid herpesviruses among different Arabian horse populations in Egypt.
- Author
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Azab W, Bedair S, Abdelgawad A, Eschke K, Farag GK, Abdel-Raheim A, Greenwood AD, Osterrieder N, and Ali AAH
- Subjects
- Animals, Egypt epidemiology, Equidae, Female, Herpesviridae Infections epidemiology, Herpesviridae Infections virology, Horse Diseases virology, Horses, Incidence, Male, Prevalence, Herpesviridae isolation & purification, Herpesviridae Infections veterinary, Horse Diseases epidemiology
- Abstract
Equid herpesviruses (EHVs) threaten equine health and can cause significant economic losses to the equine industry worldwide. Different equid herpesviruses, EHV-1, EHV-2, EHV-4 and EHV5 are regularly detected among horse populations. In Egypt, monitoring is sporadic but EHV-1 or EHV-4 have been reported to circulate in the horse population. However, there is a lack of reports related to infection and health status of horses, likely due to the absence of regular diagnostic procedures. In the current study, the circulation of four infectious equid herpesviruses (EHV-1, EHV-2, EHV-4 and EHV-5) among different Arabian horse populations and donkeys residing the same farm was monitored. Different samples were collected and DNA was extracted and subjected to quantitative (q)-PCR to detect the four equid herpesviruses using specific primers and probes. Antibody titres against EHV-1 and EHV-4 were tested using virus neutralization test and type-specific ELISA. The results showed that EHV-1, EHV-2, EHV-4 and EHV-5 are endemic and can be a continuous threat for horses in the absence of vaccination programs and frequent virus reactivation. There is an urgent need for introduction of active regular surveillance measures to investigate the presence of different equid herpesviruses, and other equine viral pathogens, in various horse populations around Egypt and to establish a standardized cataloguing of equine health status., (© 2019 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)
- Published
- 2019
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41. EHV-1 Pathogenesis: Current in vitro Models and Future Perspectives.
- Author
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Kamel M, Pavulraj S, Osterrieder K, and Azab W
- Abstract
Primary infection and pathogenesis of equine herpesvirus type 1 (EHV-1) require an intricate interaction of virus with the mucosal epithelium, mononuclear cells and the vascular endothelium. Studies on EHV-1 have been facilitated by the development of different in vitro models that recapitulate the in vivo tissue complexity. The available in vitro assays can be categorized into (i) models mimicking the epithelium-peripheral blood mononuclear cell (PBMC) interaction, which include ex vivo mucosal (nasal and vaginal) explants and equine respiratory epithelial cells (EREC) cultures; and (ii) PBMC-endothelium mimicking models, including flow chamber and contact assays. These in vitro models have proven their worth in attempts to recapitulate the in vivo architecture and complexity, produce data relevant to natural host infection, and reduce animal use due to in vivo experiments. Although horse models are still needed for certain experiments, e.g., EHV-1 myeloencephalopathy or vaccination studies, available in vitro models can be used to obtain highly valuable data on virus-host tissue interactions. Microfluidic based 3D culture system (e.g., horse-on-a-chip) could be a potential upgraded version of these in vitro models for future research.
- Published
- 2019
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42. Equine Herpesvirus 1 Bridles T Lymphocytes To Reach Its Target Organs.
- Author
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Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Couck L, Van den Broeck W, Azab W, and Nauwynck HJ
- Subjects
- Animals, Cells, Cultured, Endothelial Cells immunology, Endothelial Cells virology, Epithelial Cells immunology, Epithelial Cells virology, Herpesviridae Infections virology, Horse Diseases virology, Horses virology, Immune Evasion immunology, Monocytes immunology, Monocytes virology, Respiratory Mucosa immunology, Respiratory Mucosa virology, T-Lymphocytes virology, Viral Proteins immunology, Viremia immunology, Viremia virology, Virus Replication immunology, Herpesviridae Infections immunology, Herpesvirus 1, Equid immunology, Horse Diseases immunology, Horses immunology, T-Lymphocytes immunology
- Abstract
Equine herpesvirus 1 (EHV1) replicates in the respiratory epithelium and disseminates through the body via a cell-associated viremia in leukocytes, despite the presence of neutralizing antibodies. "Hijacked" leukocytes, previously identified as monocytic cells and T lymphocytes, transmit EHV1 to endothelial cells of the endometrium or central nervous system, causing reproductive (abortigenic variants) or neurological (neurological variants) disorders. In the present study, we questioned the potential route of EHV1 infection of T lymphocytes and how EHV1 misuses T lymphocytes as a vehicle to reach the endothelium of the target organs in the absence or presence of immune surveillance. Viral replication was evaluated in activated and quiescent primary T lymphocytes, and the results demonstrated increased infection of activated versus quiescent, CD4
+ versus CD8+ , and blood- versus lymph node-derived T cells. Moreover, primarily infected respiratory epithelial cells and circulating monocytic cells efficiently transferred virions to T lymphocytes in the presence of neutralizing antibodies. Albeit T-lymphocytes express all classes of viral proteins early in infection, the expression of viral glycoproteins on their cell surface was restricted. In addition, the release of viral progeny was hampered, resulting in the accumulation of viral nucleocapsids in the T cell nucleus. During contact of infected T lymphocytes with endothelial cells, a late viral protein(s) orchestrates T cell polarization and synapse formation, followed by anterograde dynein-mediated transport and transfer of viral progeny to the engaged cell. This represents a sophisticated but efficient immune evasion strategy to allow transfer of progeny virus from T lymphocytes to adjacent target cells. These results demonstrate that T lymphocytes are susceptible to EHV1 infection and that cell-cell contact transmits infectious virus to and from T lymphocytes. IMPORTANCE Equine herpesvirus 1 (EHV1) is an ancestral alphaherpesvirus that is related to herpes simplex virus 1 and causes respiratory, reproductive, and neurological disorders in Equidae. EHV1 is indisputably a master at exploiting leukocytes to reach its target organs, accordingly evading the host immunity. However, the role of T lymphocytes in cell-associated viremia remains poorly understood. Here we show that activated T lymphocytes efficiently become infected and support viral replication despite the presence of protective immunity. We demonstrate a restricted expression of viral proteins on the surfaces of infected T cells, which prevents immune recognition. In addition, we indicate a hampered release of progeny, which results in the accumulation of nucleocapsids in the T cell nucleus. Upon engagement with the target endothelium, late viral proteins orchestrate viral synapse formation and viral transfer to the contact cell. Our findings have significant implications for the understanding of EHV1 pathogenesis, which is essential for developing innovative therapies to prevent the devastating clinical symptoms of infection., (Copyright © 2019 Poelaert et al.)- Published
- 2019
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43. How Host Specific Are Herpesviruses? Lessons from Herpesviruses Infecting Wild and Endangered Mammals.
- Author
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Azab W, Dayaram A, Greenwood AD, and Osterrieder N
- Subjects
- Animals, Disease Transmission, Infectious, Herpesviridae Infections transmission, Herpesviridae Infections virology, Herpesviridae growth & development, Herpesviridae Infections veterinary, Host Specificity, Host-Pathogen Interactions
- Abstract
Herpesviruses are ubiquitous and can cause disease in all classes of vertebrates but also in animals of lower taxa, including molluscs. It is generally accepted that herpesviruses are primarily species specific, although a species can be infected by different herpesviruses. Species specificity is thought to result from host-virus coevolutionary processes over the long term. Even with this general concept in mind, investigators have recognized interspecies transmission of several members of the Herpesviridae family, often with fatal outcomes in non-definitive hosts-that is, animals that have no or only a limited role in virus transmission. We here summarize herpesvirus infections in wild mammals that in many cases are endangered, in both natural and captive settings. Some infections result from herpesviruses that are endemic in the species that is primarily affected, and some result from herpesviruses that cause fatal disease after infection of non-definitive hosts. We discuss the challenges of such infections in several endangered species in the absence of efficient immunization or therapeutic options.
- Published
- 2018
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44. Novel Divergent Polar Bear-Associated Mastadenovirus Recovered from a Deceased Juvenile Polar Bear.
- Author
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Dayaram A, Tsangaras K, Pavulraj S, Azab W, Groenke N, Wibbelt G, Sicks F, Osterrieder N, and Greenwood AD
- Subjects
- Adenoviridae Infections virology, Animal Structures virology, Animals, Animals, Zoo, Berlin, Genome, Viral, Mastadenovirus genetics, Mastadenovirus growth & development, Real-Time Polymerase Chain Reaction, Sequence Analysis, DNA, Virus Cultivation, Virus Replication, Adenoviridae Infections veterinary, Mastadenovirus classification, Mastadenovirus isolation & purification, Ursidae virology
- Abstract
Polar bears in captivity can be exposed to opportunistic pathogens not present in their natural environments. A 4-month-old polar bear ( Ursus maritimus ) living in an isolated enclosure with his mother in the Tierpark Berlin, Berlin, Germany, was suffering from severe abdominal pain, mild diarrhea, and loss of appetite and died in early 2017. Histopathology revealed severe hepatic degeneration and necrosis without evidence of inflammation or inclusion bodies, although a viral infection had been suspected on the basis of the clinical signs. We searched for nucleic acids of pathogens by shotgun high-throughput sequencing (HTS) from genomic DNA and cDNA extracted from tissue and blood. We identified a novel Mastadenovirus and assembled a nearly complete genome from the shotgun sequences. Quantitative PCR (qPCR) revealed that viral DNA was present in various concentrations in all tissues examined and that the highest concentrations were found in blood. Viral culture did not yield cytopathic effects, but qPCR suggested that virus replication was sustained for up to three passages. Positive immunofluorescence staining confirmed that the virus was able to replicate in the cells during early passage. Phylogenetic analysis demonstrated that the virus is highly divergent compared to other previously identified Mastadenovirus members and basal to most known viral clades. The virus was found only in the 4-month-old bear and not in other captive polar bears tested. We surmised, therefore, that the polar bear was infected from an unknown reservoir, illustrating that adenoviral diversity remains underestimated and that cross-species transmission of viruses can occur even under conditions of relative isolation. IMPORTANCE Cross-species transmission of viral pathogens is becoming an increasing problem for captive-animal facilities. This study highlights how animals in captivity are vulnerable to novel opportunistic pathogens, many of which do not result in straightforward diagnosis from symptoms and histopathology. In this study, a novel pathogen was suspected to have contributed to the death of a juvenile polar bear. HTS techniques were employed, and a novel Mastadenovirus was isolated. The virus was present in both the tissue and blood samples. Phylogenetic analysis of the virus at both the gene and genome levels revealed that it is highly divergent to other known mastadenoviruses. Overall, this study shows that animals in isolated conditions still come into contact with novel pathogens, and for many of these pathogens, the host reservoir and mode of transmission are yet to be determined., (Copyright © 2018 Dayaram et al.)
- Published
- 2018
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45. Multivalent Flexible Nanogels Exhibit Broad-Spectrum Antiviral Activity by Blocking Virus Entry.
- Author
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Dey P, Bergmann T, Cuellar-Camacho JL, Ehrmann S, Chowdhury MS, Zhang M, Dahmani I, Haag R, and Azab W
- Subjects
- Animals, Cell Line, Chlorocebus aethiops, Click Chemistry, Heparan Sulfate Proteoglycans analogs & derivatives, Heparan Sulfate Proteoglycans pharmacology, Herpes Simplex drug therapy, Herpesvirus 1, Human drug effects, Humans, Models, Molecular, Nanoparticles chemistry, Vero Cells, Antiviral Agents chemistry, Antiviral Agents pharmacology, Gels chemistry, Gels pharmacology, Glycerol chemistry, Glycerol pharmacology, Polymers chemistry, Polymers pharmacology, Virus Internalization drug effects
- Abstract
The entry process of viruses into host cells is complex and involves stable but transient multivalent interactions with different cell surface receptors. The initial contact of several viruses begins with attachment to heparan sulfate (HS) proteoglycans on the cell surface, which results in a cascade of events that end up with virus entry. The development of antiviral agents based on multivalent interactions to shield virus particles and block initial interactions with cellular receptors has attracted attention in antiviral research. Here, we designed nanogels with different degrees of flexibility based on dendritic polyglycerol sulfate to mimic cellular HS. The designed nanogels are nontoxic and broad-spectrum, can multivalently interact with viral glycoproteins, shield virus surfaces, and efficiently block infection. We also visualized virus-nanogel interactions as well as the uptake of nanogels by the cells through clathrin-mediated endocytosis using confocal microscopy. As many human viruses attach to the cells through HS moieties, we introduce our flexible nanogels as robust inhibitors for these viruses.
- Published
- 2018
- Full Text
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46. Physiological costs of infection: herpesvirus replication is linked to blood oxidative stress in equids.
- Author
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Costantini D, Seeber PA, Soilemetzidou SE, Azab W, Bohner J, Buuveibaatar B, Czirják GÁ, East ML, Greunz EM, Kaczensky P, Lamglait B, Melzheimer J, Uiseb K, Ortega A, Osterrieder N, Sandgreen DM, Simon M, Walzer C, and Greenwood AD
- Subjects
- Animals, DNA, Viral genetics, DNA, Viral metabolism, Equidae, Female, Glutathione Peroxidase metabolism, Herpesviridae genetics, Herpesviridae isolation & purification, Herpesviridae Infections veterinary, Herpesviridae Infections virology, Horses, Least-Squares Analysis, Male, Protein Carbonylation, Species Specificity, Herpesviridae physiology, Herpesviridae Infections pathology, Oxidative Stress, Virus Replication
- Abstract
Viruses may have a dramatic impact on the health of their animal hosts. The patho-physiological mechanisms underlying viral infections in animals are, however, not well understood. It is increasingly recognized that oxidative stress may be a major physiological cost of viral infections. Here we compare three blood-based markers of oxidative status in herpes positive and negative individuals of the domestic horse (Equus ferus caballus) and of both captive and free-ranging Mongolian khulan (Equus hemionus hemionus) and plains zebra (Equus quagga). Herpes positive free-ranging animals had significantly more protein oxidative damage and lower glutathione peroxidase (antioxidant enzyme) than negative ones, providing correlative support for a link between oxidative stress and herpesvirus infection in free-living equids. Conversely, we found weak evidence for oxidative stress in herpes positive captive animals. Hence our work indicates that environment (captive versus free living) might affect the physiological response of equids to herpesvirus infection. The Mongolian khulan and the plains zebra are currently classified as near threatened by the International Union for Conservation of Nature. Thus, understanding health impacts of pathogens on these species is critical to maintaining viable captive and wild populations.
- Published
- 2018
- Full Text
- View/download PDF
47. Subclinical infection of a young captive Asian elephant with elephant endotheliotropic herpesvirus 1.
- Author
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Azab W, Damiani AM, Ochs A, and Osterrieder N
- Subjects
- Animals, Asymptomatic Infections, Female, Herpesviridae classification, Herpesviridae genetics, Herpesviridae Infections virology, Elephants virology, Herpesviridae isolation & purification, Herpesviridae Infections veterinary
- Abstract
Elephant endotheliotropic herpesviruses (EEHVs) are a continuous threat for young Asian elephants. We report a laboratory-confirmed infection of a 5-year-old female Asian elephant (AZ_2016) in the Berlin Zoologischer Garten. Initially, high EEHV-1 loads were detected in trunk swabs obtained from the young elephant during routine screening. The animal showed no clinical signs except for slight irritability. EEHV-1 was continuously shed for almost one year, with fluctuations in viral load from time to time. Our investigations highlight the continuous threat of EEHV-1 to young captive Asian elephants and stress the importance of routine monitoring of captive elephants to allow early detection of infection.
- Published
- 2018
- Full Text
- View/download PDF
48. Viral genes and cellular markers associated with neurological complications during herpesvirus infections.
- Author
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Holz CL, Nelli RK, Wilson ME, Zarski LM, Azab W, Baumgardner R, Osterrieder N, Pease A, Zhang L, Hession S, Goehring LS, Hussey SB, and Soboll Hussey G
- Subjects
- Animals, Female, Herpesviridae Infections pathology, Horses, Male, Models, Animal, Virulence Factors metabolism, Biomarkers analysis, Encephalitis, Viral pathology, Herpesviridae Infections complications, Herpesviridae Infections virology, Herpesvirus 1, Equid pathogenicity, Host-Pathogen Interactions, Viral Proteins metabolism
- Abstract
Despite the importance of neurological disorders associated with herpesviruses, the mechanism by which these viruses influence the central nervous system (CNS) has not been definitively established. Owing to the limitations of studying neuropathogenicity of human herpesviruses in their natural host, many aspects of their pathogenicity and immune response are studied in animal models. Here, we present an important model system that enables studying neuropathogenicity of herpesviruses in the natural host. Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus that causes a devastating neurological disease (EHV-1 myeloencephalopathy; EHM) in horses. Like other alphaherpesviruses, our understanding of virus neuropathogenicity in the natural host beyond the essential role of viraemia is limited. In particular, information on the role of different viral proteins for virus transfer to the spinal cord endothelium in vivo is lacking. In this study, the contribution of two viral proteins, DNA polymerase (ORF30) and glycoprotein D (gD), to the pathogenicity of EHM was addressed. Furthermore, different cellular immune markers, including alpha-interferon (IFN-α), gamma-interferon (IFN-γ), interleukin-10 (IL-10) and interleukin-1 beta (IL-1β), were identified to play a role during the course of the disease.
- Published
- 2017
- Full Text
- View/download PDF
49. Initial Contact: The First Steps in Herpesvirus Entry.
- Author
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Azab W and Osterrieder K
- Subjects
- Animals, Glycoproteins metabolism, Humans, Receptors, Virus metabolism, Signal Transduction, Viral Proteins metabolism, Herpesviridae physiology, Virus Internalization
- Abstract
The entry process of herpesviruses into host cells is complex and highly variable. It involves a sequence of well-orchestrated events that begin with virus attachment to glycan-containing proteinaceous structures on the cell surface. This initial contact tethers virus particles to the cell surface and results in a cascade of molecular interactions, including the tight interaction of viral envelope glycoproteins to specific cell receptors. These interactions trigger intracellular signaling and finally virus penetration after fusion of the viral envelope with cellular membranes. Based on the engaged cellular receptors and co-receptors, and the subsequent signaling cascades, the entry pathway will be decided on the spot. A number of viral glycoproteins and many cellular receptors and molecules have been identified as players in one or several of these events during virus entry. This chapter will review viral glycoproteins, cellular receptors and signaling cascades associated with the very first interactions of herpesviruses with their target cells.
- Published
- 2017
- Full Text
- View/download PDF
50. The Role of the Equine Herpesvirus Type 1 (EHV-1) US3-Encoded Protein Kinase in Actin Reorganization and Nuclear Egress.
- Author
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Proft A, Spiesschaert B, Izume S, Taferner S, Lehmann MJ, and Azab W
- Subjects
- Cell Line, Gene Knockout Techniques, Herpesvirus 1, Equid growth & development, Humans, Protein Serine-Threonine Kinases genetics, Viral Plaque Assay, Viral Proteins genetics, Viral Proteins metabolism, Actins metabolism, Herpesvirus 1, Equid enzymology, Herpesvirus 1, Equid physiology, Host-Pathogen Interactions, Protein Serine-Threonine Kinases metabolism, Virus Release
- Abstract
The serine-threonine protein kinase encoded by US3 gene (pUS3) of alphaherpesviruses was shown to modulate actin reorganization, cell-to-cell spread, and virus egress in a number of virus species. However, the role of the US3 orthologues of equine herpesvirus type 1 and 4 (EHV-1 and EHV-4) has not yet been studied. Here, we show that US3 is not essential for virus replication in vitro. However, growth rates and plaque diameters of a US3 -deleted EHV-1 and a mutant in which the catalytic active site was destroyed were significantly reduced when compared with parental and revertant viruses or a virus in which EHV-1 US3 was replaced with the corresponding EHV-4 gene. The reduced plaque sizes were consistent with accumulation of primarily enveloped virions in the perinuclear space of the US3 -negative EHV-1, a phenotype that was also rescued by the EHV-4 orthologue. Furthermore, actin stress fiber disassembly was significantly more pronounced in cells infected with parental EHV-1, revertant, or the recombinant EHV-1 expressing EHV-4 US3 . Finally, we observed that deletion of US3 in EHV-1 did not affect the expression of adhesion molecules on the surface of infected cells., Competing Interests: The authors declare no conflict of interest.
- Published
- 2016
- Full Text
- View/download PDF
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