Subclinical infection of macaques and baboons with a baboon simartevirus

Abstract

Simarteviruses (Arteriviridae: Simartevirus) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simartevirus pathogenesis by infecting olive baboons (n=4) and rhesus macaques (n=4) with the simartevirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1x107 and 1x108 vRNA copies/ml at 3-10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1x106 and 1x107 vRNA copies/ml for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simartevirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies.\n\nOne Sentence SummarySimartevirus infection has multiple disease manifestations following cross-species transmission.\n\nAccessible Summary/ImportanceSimarteviruses are known to infect African monkeys, such as olive baboons, without causing overt disease. In contrast, accidental infection of Asian monkeys, such as rhesus monkeys, has resulted in severe and often fatal disease. We used a simartevirus found circulating among captive olive baboons (Southwest baboon virus 1; SWBV-1) to experimentally infect both olive baboons and rhesus monkeys to model infection with the same virus in both natural and non-natural hosts. Surprisingly, neither baboons nor macaques displayed any laboratory abnormalities or signs of disease over the course of infection, despite robust SWBV-1 replication. In the accompanying study by Cornish et al., a similar experimental approach was undertaken: African patas monkeys and rhesus monkeys were infected with the simartevirus simian hemorrhagic fever virus (SHFV). In contrast to our study, SHFV caused disease in both of these hosts, albeit with much more severe disease developing in the macaques. Interestingly, we observed similar levels of immune cell activation in simartevirus-infected animals across both studies, suggesting that finer nuances of the host response, and perhaps properties of each individual simartevirus, may influences pathogenicity of these viruses in primates. Taken together, our collective findings highlight the wide clinical spectrum of simartevirus infection, ranging from highly-lethal hemorrhagic disease to persistent infection without any overt signs of disease, even in non-natural primate hosts.