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A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection.
PLoS Pathog
June 2022
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-based trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting. Despite extensive analysis, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which this signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY), replicates acutely to high levels in pigtail macaques (PTM) but is rapidly controlled.
View Article and Find Full Text PDFIFN-α blockade during ART-treated SIV infection lowers tissue vDNA, rescues immune function, and improves overall health.
JCI Insight
March 2022
Division of Experimental Medicine, University of California, San Francisco, San Francisco, California, USA.
Type I IFNs (TI-IFNs) drive immune effector functions during acute viral infections and regulate cell cycling and systemic metabolism. That said, chronic TI-IFN signaling in the context of HIV infection treated with antiretroviral therapy (ART) also facilitates viral persistence, in part by promoting immunosuppressive responses and CD8+ T cell exhaustion. To determine whether inhibition of IFN-α might provide benefit in the setting of chronic, ART-treated SIV infection of rhesus macaques, we administered an anti-IFN-α antibody followed by an analytical treatment interruption (ATI).
View Article and Find Full Text PDFGammaherpesvirus infection and malignant disease in rhesus macaques experimentally infected with SIV or SHIV.
PLoS Pathog
July 2018
AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland, United States of America.
Human gammaherpesviruses are associated with malignancies in HIV infected individuals; in macaques used in non-human primate models of HIV infection, gammaherpesvirus infections also occur. Limited data on prevalence and tumorigenicity of macaque gammaherpesviruses, mostly cross-sectional analyses of small series, are available. We comprehensively examine all three-rhesus macaque gammaherpesviruses -Rhesus rhadinovirus (RRV), Rhesus Lymphocryptovirus (RLCV) and Retroperitoneal Fibromatosis Herpesvirus (RFHV) in macaques experimentally infected with Simian Immunodeficiency Virus or Simian Human Immunodeficiency Virus (SIV/SHIV) in studies spanning 15 years at the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research.
View Article and Find Full Text PDFEarly Sites of Virus Replication After Oral SIV Infection of Infant Macaques: Implications for Pathogenesis.
AIDS Res Hum Retroviruses
March 2018
2 Department of Microbiology and Immunology and Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Despite optimization of preventative measures for vertical HIV-1 transmission, daily, roughly 400 infants become HIV infected, most of them through breastfeeding. Viral entry has been presumed to occur in the gastrointestinal tract; however, the exact entry site(s) have not been defined. Therefore, we quantified simian immunodeficiency virus (SIV) RNA and DNA in oral, intestinal, and systemic tissues of 15 infant macaques within 48-96 h after oral SIV exposure.
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