Moncla Louise H, Weiler Andrea M, Barry Gabrielle, Weinfurter Jason T, Dinis Jorge M, Charlier Olivia, Lauck Michael, Bailey Adam L, Wahl-Jensen Victoria, Nelson Chase W, Johnson Joshua C, Caì Yíngyún, Goldberg Tony L, O'Connor David H, Jahrling Peter B, Kuhn Jens H, Friedrich Thomas C
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Microbiology Doctoral Training Program, University of Wisconsin, Madison, Wisconsin, USA.
J Virol. 2017 Jan 31;91(4). doi: 10.1128/JVI.02231-16. Print 2017 Feb 15.
Simian arteriviruses are a diverse clade of viruses infecting captive and wild nonhuman primates. We recently reported that Kibale red colobus virus 1 (KRCV-1) causes a mild and self-limiting disease in experimentally infected crab-eating macaques, while simian hemorrhagic fever virus (SHFV) causes lethal viral hemorrhagic fever. Here we characterize how these viruses evolved during replication in cell culture and in experimentally infected macaques. During passage in cell culture, 68 substitutions that were localized in open reading frames (ORFs) likely associated with host cell entry and exit became fixed in the KRCV-1 genome. However, we did not detect any strong signatures of selection during replication in macaques. We uncovered patterns of evolution that were distinct from those observed in surveys of wild red colobus monkeys, suggesting that these species may exert different adaptive challenges for KRCV-1. During SHFV infection, we detected signatures of selection on ORF 5a and on a small subset of sites in the genome. Overall, our data suggest that patterns of evolution differ markedly among simian arteriviruses and among host species.
Certain RNA viruses can cross species barriers and cause disease in new hosts. Simian arteriviruses are a diverse group of related viruses that infect captive and wild nonhuman primates, with associated disease severity ranging from apparently asymptomatic infections to severe, viral hemorrhagic fevers. We infected nonhuman primate cell cultures and then crab-eating macaques with either simian hemorrhagic fever virus (SHFV) or Kibale red colobus virus 1 (KRCV-1) and assessed within-host viral evolution. We found that KRCV-1 quickly acquired a large number of substitutions in its genome during replication in cell culture but that evolution in macaques was limited. In contrast, we detected selection focused on SHFV ORFs 5a and 5, which encode putative membrane proteins. These patterns suggest that in addition to diverse pathogenic phenotypes, these viruses may also exhibit distinct patterns of within-host evolution both in vitro and in vivo.
猿猴动脉炎病毒是一类多样的病毒，可感染圈养和野生的非人灵长类动物。我们最近报道，基巴莱红疣猴病毒1（KRCV-1）在实验感染的食蟹猕猴中引起轻度自限性疾病，而猴出血热病毒（SHFV）则引起致命的病毒性出血热。在此，我们描述了这些病毒在细胞培养和实验感染的猕猴体内复制过程中的进化情况。在细胞培养传代过程中，68个位于可能与宿主细胞进出相关的开放阅读框（ORF）中的替换在KRCV-1基因组中固定下来。然而，我们在猕猴体内复制过程中未检测到任何强烈的选择特征。我们发现了与野生红疣猴调查中观察到的不同的进化模式，这表明这些物种可能对KRCV-1施加不同的适应性挑战。在SHFV感染期间，我们在ORF 5a和基因组中的一小部分位点检测到选择特征。总体而言，我们的数据表明，猿猴动脉炎病毒之间以及宿主物种之间的进化模式存在显著差异。
某些RNA病毒可跨越物种屏障并在新宿主中引起疾病。猿猴动脉炎病毒是一组多样的相关病毒，可感染圈养和野生的非人灵长类动物，相关疾病严重程度从明显无症状感染到严重的病毒性出血热不等。我们用猴出血热病毒（SHFV）或基巴莱红疣猴病毒1（KRCV-1）感染非人灵长类细胞培养物，然后感染食蟹猕猴，并评估宿主内病毒进化。我们发现，KRCV-1在细胞培养复制过程中其基因组迅速获得大量替换，但在猕猴体内的进化有限。相比之下，我们检测到选择集中在SHFV的ORF 5a和5上，它们编码假定的膜蛋白。这些模式表明，除了多样的致病表型外，这些病毒在体外和体内的宿主内进化模式也可能不同。
