Hahn, Alexander S.

[["dc.bibliographiccitation.artnumber","e01093-19"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Virology"],["dc.bibliographiccitation.volume","94"],["dc.contributor.author","Hahn, Alexander S."],["dc.contributor.author","Bischof, Georg F."],["dc.contributor.author","Großkopf, Anna K."],["dc.contributor.author","Shin, Young C."],["dc.contributor.author","Domingues, Aline"],["dc.contributor.author","Gonzalez-Nieto, Lucas"],["dc.contributor.author","Rakasz, Eva G."],["dc.contributor.author","Watkins, David I."],["dc.contributor.author","Ensser, Armin"],["dc.contributor.author","Martins, Mauricio A."],["dc.contributor.editor","Longnecker, Richard M."],["dc.date.accessioned","2022-10-06T13:25:34Z"],["dc.date.available","2022-10-06T13:25:34Z"],["dc.date.issued","2020"],["dc.description.abstract","Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with a substantial disease burden in sub-Saharan Africa, often in the context of human immunodeficiency virus (HIV) infection. The related rhesus monkey rhadinovirus (RRV) has shown potential as a vector to immunize monkeys with antigens from simian immunodeficiency virus (SIV), the macaque model for HIV. KSHV and RRV engage cellular receptors from the Eph family via the viral gH/gL glycoprotein complex. We have now generated a recombinant RRV that expresses the SIV Gag antigen and does not express gL. This recombinant RRV was infectious by the intravenous route, established persistent infection in the B cell compartment, and elicited strong immune responses to the SIV Gag antigen. These results argue against a role for gL and Eph family receptors in B cell infection by RRV\n in vivo\n and have implications for the development of a live-attenuated KSHV vaccine or vaccine vector."],["dc.description.abstract","ABSTRACT\n \n A replication-competent, recombinant strain of rhesus monkey rhadinovirus (RRV) expressing the Gag protein of SIVmac239 was constructed in the context of a glycoprotein L (gL) deletion mutation. Deletion of gL detargets the virus from Eph family receptors. The ability of this gL-minus Gag recombinant RRV to infect, persist, and elicit immune responses was evaluated after intravenous inoculation of two\n Mamu-A*01\n +\n RRV-naive rhesus monkeys. Both monkeys responded with an anti-RRV antibody response, and quantitation of RRV DNA in peripheral blood mononuclear cells (PBMC) by real-time PCR revealed levels similar to those in monkeys infected with recombinant gL\n +\n RRV. Comparison of RRV DNA levels in sorted CD3\n +\n versus CD20\n +\n versus CD14\n +\n PBMC subpopulations indicated infection of the CD20\n +\n subpopulation by the gL-minus RRV. This contrasts with results obtained with transformed B cell lines\n in vitro\n , in which deletion of gL resulted in markedly reduced infectivity. Over a period of 20 weeks, Gag-specific CD8\n +\n T cell responses were documented by major histocompatibility complex class I (MHC-I) tetramer staining. Vaccine-induced CD8\n +\n T cell responses, which were predominantly directed against the Mamu-A*01-restricted Gag\n 181-189\n CM9 epitope, could be inhibited by blockade of MHC-I presentation. Our results indicate that gL and the interaction with Eph family receptors are dispensable for the colonization of the B cell compartment following high-dose infection by the intravenous route, which suggests the existence of alternative receptors. Further, gL-minus RRV elicits cellular immune responses that are predominantly canonical in nature.\n \n \n IMPORTANCE\n Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with a substantial disease burden in sub-Saharan Africa, often in the context of human immunodeficiency virus (HIV) infection. The related rhesus monkey rhadinovirus (RRV) has shown potential as a vector to immunize monkeys with antigens from simian immunodeficiency virus (SIV), the macaque model for HIV. KSHV and RRV engage cellular receptors from the Eph family via the viral gH/gL glycoprotein complex. We have now generated a recombinant RRV that expresses the SIV Gag antigen and does not express gL. This recombinant RRV was infectious by the intravenous route, established persistent infection in the B cell compartment, and elicited strong immune responses to the SIV Gag antigen. These results argue against a role for gL and Eph family receptors in B cell infection by RRV\n in vivo\n and have implications for the development of a live-attenuated KSHV vaccine or vaccine vector."],["dc.description.sponsorship","IZKF Erlangen"],["dc.description.sponsorship"," HHS | National Institutes of Health https://doi.org/10.13039/100000002"],["dc.description.sponsorship"," HHS | National Institutes of Health https://doi.org/10.13039/100000002"],["dc.description.sponsorship"," HHS | National Institutes of Health https://doi.org/10.13039/100000002"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659"],["dc.description.sponsorship"," HHS | U.S. Public Health Service https://doi.org/10.13039/100007197"],["dc.identifier.doi","10.1128/JVI.01093-19"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114870"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.eissn","1098-5514"],["dc.relation.issn","0022-538X"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.rights.uri","https://journals.asm.org/non-commercial-tdm-license"],["dc.title","A Recombinant Rhesus Monkey Rhadinovirus Deleted of Glycoprotein L Establishes Persistent Infection of Rhesus Macaques and Elicits Conventional T Cell Responses"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]