Abstract
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, immune activation, or adaptive immune responses–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.
Highlights
Human pegivirus (HPgV)–formerly known as GB virus C (GBV-C) and as Hepatitis G Virus (HGV)–is a positive-sense, single-stranded RNA virus in the Pegivirus genus of the Flaviviridae family [1]
People infected with human immunodeficiency virus (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
We found that simian pegivirus (SPgV) had no impact on simian immunodeficiency virus (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
Summary
Human pegivirus (HPgV)–formerly known as GB virus C (GBV-C) and as Hepatitis G Virus (HGV)–is a positive-sense, single-stranded RNA virus in the Pegivirus genus of the Flaviviridae family [1]. HIV-infected individuals co-infected with HPgV are protected from HIV-induced CD4 T cell depletion [5,6,7,8] and pathological immune activation [9,10,11,12]. These individuals experience a 2.5-fold reduction in all-cause mortality relative to HIV+ individuals not co-infected with HPgV (see [13] for a meta-analysis and [2] for a review). The impact of HPgV co-infection on the natural course of HIV infection, and the mechanism(s) by which HPgV attenuates HIV disease in vivo, remain largely uncharacterized
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