TY - JOUR T1 - Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection JF - bioRxiv DO - 10.1101/175646 SP - 175646 AU - Adam L. Bailey AU - Connor R. Buechler AU - Daniel R. Matson AU - Eric J. Peterson AU - Kevin G. Brunner AU - Mariel S. Mohns AU - Meghan Breitbach AU - Laurel M. Stewart AU - Adam J. Ericsen AU - Saverio Capuano III AU - Heather A. Simmons AU - David T. Yang AU - David H. O’Connor Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/08/13/175646.abstract N2 - Human pegivirus (HPgV) protects HIV+ people from HIV-associated disease, but the mechanism of this protective effect remains poorly understood. We sequentially infected cynomolgus macaques with simian pegivirus (SPgV) and simian immunodeficiency virus (SIV) to model HIV+HPgV co-infection. SPgV had no effect on acute-phase SIV pathogenesis – as measured by SIV viral load, CD4+ T cell destruction, and immune activation – suggesting that HPgV’s protective effect is exerted primarily during the chronic phase of HIV infection. We also examined the immune response to SPgV in unprecedented detail, and found that this virus elicits virtually no activation of the immune system despite persistently high titers in the blood over long periods of time. Overall, this study expands our understanding of the pegiviruses – an understudied group of viruses with a high prevalence in the global human population – and suggests that the protective effect observed in HIV+HPgV co-infected people occurs primarily during the chronic phase of HIV infection.One Sentence Summary Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection.Short Title Pegivirus and AIDS-virus co-infectionAccessible Summary People infected with HIV live longer, healthier lives when they are co-infected with the human pegivirus (HPgV) – an understudied virus with a high prevalence in the global human population. To better understand how HPgV protects people with HIV from HIV-associated disease, we infected macaques with simian versions of these two viruses (SPgV and SIV). We found that SPgV had no impact on the incidence of SIV-associated disease early during the course of SIV infection – a time when SIV and HIV are known to cause irreversible damage to the immune system. Oddly, we found that the immune system did not recognize SPgV; a finding that warrants further investigation. Overall, this study greatly expands on our understanding of the pegiviruses and their interaction with the immune system. ER -