Breitbach, M. | Search bioRxiv

bioRxiv2017

Infection via mosquito bite alters Zika virus replication kinetics in rhesus macaques

For more than three decades it has been recognized that small amounts of vector saliva can significantly alter the infectivity of vector-borne pathogens and subsequent in vivo dynamics. Mouse and nonhuman primate models now serve as useful platforms to study Zika virus (ZIKV) pathogenesis, candidate therapies, and vaccines, but they rely on needle inoculation of virus: the effects of mosquito-borne infection on disease outcome have not been explored in these models. To model vector-borne transmission of ZIKV in nonhuman primates, we infected Aedes aegypti mosquitoes with ZIKV and allowed them to feed on four ZIKV-naive rhesus macaques. We compared ZIKV replication kinetics and tissue distribution between animals that were subcutaneously inoculated with 104 plaque-forming units of ZIKV and those that were exposed via mosquito bite. Here, we show that infection via mosquito bite delays ZIKV replication to peak viral loads in rhesus macaques. Importantly, in mosquito-infected animals ZIKV tissue distribution was limited to hemolymphatic tissues, female reproductive tract tissues, kidney, and liver, potentially emulating key features of human ZIKV infections, most of which are characterized by mild or asymptomatic disease. This newly developed system will be valuable for studying ZIKV disease because it more closely mimics human infection by mosquito bite than needle-based inoculations.

microbiology↗

bioRxiv2017

Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection

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 HPgVs 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.\n\nOne Sentence SummaryPegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection.\n\nShort TitlePegivirus and AIDS-virus co-infection\n\nAccessible SummaryPeople 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.

immunology↗