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dc.contributor.authorMuniraju, Murali
dc.contributor.authorMutsvunguma, Lorraine Z.
dc.contributor.authorFoley, Joslyn
dc.contributor.authorEscalante, Gabriela M.
dc.contributor.authorRodriguez, Esther
dc.contributor.authorNabiee, Romina
dc.contributor.authorTotonchy, Jennifer
dc.contributor.authorMulama, David H.
dc.contributor.authorNyagol, Joshua
dc.contributor.authorWussow, Felix
dc.contributor.authorBarasa, Anne K.
dc.contributor.authorBrehm, Michael A.
dc.contributor.authorOgembo, Javier Gordon
dc.date2022-08-11T08:10:17.000
dc.date.accessioned2022-08-23T17:03:14Z
dc.date.available2022-08-23T17:03:14Z
dc.date.issued2019-05-29
dc.date.submitted2019-07-08
dc.identifier.citation<p>J Virol. 2019 May 29. pii: JVI.00630-19. doi: 10.1128/JVI.00630-19. [Epub ahead of print] <a href="https://doi.org/10.1128/JVI.00630-19">Link to article on publisher's site</a></p>
dc.identifier.issn0022-538X (Linking)
dc.identifier.doi10.1128/JVI.00630-19
dc.identifier.pmid31142670
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44383
dc.description.abstractKaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and is the causative infectious agent of Kaposi sarcoma and two malignancies of B cell origin. To date, there is no licensed KSHV vaccine. Development of an effective vaccine against KSHV continues to be limited by a poor understanding of how the virus initiates acute primary infection in vivo in diverse human cell types. The role of glycoprotein H (gH) in herpesvirus entry mechanisms remains largely unresolved. To characterize the requirement for KSHV gH in the viral life cycle and in determination of cell tropism, we generated and characterized a mutant KSHV in which expression of gH was abrogated. Using a bacterial artificial chromosome containing a complete recombinant KSHV genome and recombinant DNA technology, we inserted stop codons into the gH coding region. We used electron microscopy to reveal that the gH-null mutant virus assembled and exited from cells normally, compared to wild-type virus. Using purified virions, we assessed infectivity of the gH-null mutant in diverse mammalian cell types in vitro Unlike wild-type virus or a gH-containing revertant, the gH-null mutant was unable to infect any of the epithelial, endothelial, or fibroblast cell types tested. However, its ability to infect B cells was equivocal, and remains to be investigated in vivo due to generally poor infectivity in vitro Together, these results suggest that gH is critical for KSHV infection of highly permissive cell types including epithelial, endothelial, and fibroblasts. MPORTANCE: All homologues of herpesvirus gH studied to date have been implicated in playing an essential role in viral infection of diverse permissive cell types. However, the role of gH in the mechanism of KSHV infection remains largely unresolved. In this study, we generated a gH-null mutant KSHV and provided evidence that deficiency of gH expression did not affect viral particle assembly or egress. Using the gH-null mutant, we showed that gH was indispensable for KSHV infection of epithelial, endothelial, and fibroblast cells in vitro. This suggests that gH is an important target for the development of a KSHV prophylactic vaccine to prevent initial viral infection.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31142670&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2019 American Society for Microbiology. Accepted manuscript posted as allowed by publisher's author rights policy at https://journals.asm.org/content/statement-author-rights.
dc.subjectKaposi sarcoma-associated herpesvirus
dc.subjectglycoprotein H
dc.subjectmutation
dc.subjectviral entry
dc.subjectinfection
dc.subjecttropism
dc.subjectepithelial
dc.subjectendothelial
dc.subjectfibroblast
dc.subjectB cell
dc.subjectcancer
dc.subjectvaccine
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectImmunology of Infectious Disease
dc.subjectImmunopathology
dc.subjectImmunoprophylaxis and Therapy
dc.subjectVirology
dc.subjectVirus Diseases
dc.subjectViruses
dc.titleKaposi Sarcoma-associated Herpesvirus Glycoprotein H is Indispensable for Infection of Epithelial, Endothelial, and Fibroblast Cell Types
dc.typeAccepted Manuscript
dc.source.journaltitleJournal of virology
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1109&amp;context=pmm_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pmm_pp/110
dc.identifier.contextkey14880302
refterms.dateFOA2022-08-23T17:03:15Z
html.description.abstract<p>Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and is the causative infectious agent of Kaposi sarcoma and two malignancies of B cell origin. To date, there is no licensed KSHV vaccine. Development of an effective vaccine against KSHV continues to be limited by a poor understanding of how the virus initiates acute primary infection in vivo in diverse human cell types. The role of glycoprotein H (gH) in herpesvirus entry mechanisms remains largely unresolved. To characterize the requirement for KSHV gH in the viral life cycle and in determination of cell tropism, we generated and characterized a mutant KSHV in which expression of gH was abrogated. Using a bacterial artificial chromosome containing a complete recombinant KSHV genome and recombinant DNA technology, we inserted stop codons into the gH coding region. We used electron microscopy to reveal that the gH-null mutant virus assembled and exited from cells normally, compared to wild-type virus. Using purified virions, we assessed infectivity of the gH-null mutant in diverse mammalian cell types in vitro Unlike wild-type virus or a gH-containing revertant, the gH-null mutant was unable to infect any of the epithelial, endothelial, or fibroblast cell types tested. However, its ability to infect B cells was equivocal, and remains to be investigated in vivo due to generally poor infectivity in vitro Together, these results suggest that gH is critical for KSHV infection of highly permissive cell types including epithelial, endothelial, and fibroblasts.</p> <p>MPORTANCE: All homologues of herpesvirus gH studied to date have been implicated in playing an essential role in viral infection of diverse permissive cell types. However, the role of gH in the mechanism of KSHV infection remains largely unresolved. In this study, we generated a gH-null mutant KSHV and provided evidence that deficiency of gH expression did not affect viral particle assembly or egress. Using the gH-null mutant, we showed that gH was indispensable for KSHV infection of epithelial, endothelial, and fibroblast cells in vitro. This suggests that gH is an important target for the development of a KSHV prophylactic vaccine to prevent initial viral infection.</p>
dc.identifier.submissionpathpmm_pp/110
dc.contributor.departmentProgram in Molecular Medicine


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