title: Within-Host Evolution of Simian Arteriviruses in Crab-Eating Macaques.
abstract: 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.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.|Microbiology Doctoral Training Program, University of Wisconsin, Madison, Wisconsin, USA.|Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Louise H
authors.initials: LH
authors.lastname: Moncla
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Weiler
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Barry
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Weinfurter
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.|Microbiology Doctoral Training Program, University of Wisconsin, Madison, Wisconsin, USA.|Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Dinis
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Charlier
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.|Microbiology Doctoral Training Program, University of Wisconsin, Madison, Wisconsin, USA.|Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lauck
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, USA.|Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Bailey
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Wahl-Jensen
authors.affiliation: Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, New York, USA.
authors.forename: Chase W
authors.initials: CW
authors.lastname: Nelson
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Johnson
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
authors.forename: Yíngyún
authors.initials: Y
authors.lastname: Caì
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.|Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Tony L
authors.initials: TL
authors.lastname: Goldberg
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA.|Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
authors.forename: Jens H
authors.identifier: http://orcid.org/0000-0002-7800-6045
authors.initials: JH
authors.lastname: Kuhn
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA thomasf@primate.wisc.edu.|Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
mesh_terms: D000818:Animals; D018018:Arterivirus / Q000502:physiology*; D018174:Arterivirus Infections / Q000662:veterinary*; D005075:Biological Evolution; D054884:Host-Pathogen Interactions / Q000235:genetics; D008252:Macaca fascicularis; D008992:Monkey Diseases / Q000235:genetics / Q000821:virology*; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral; D012641:Selection, Genetic; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D012367:RNA, Viral
keywords: evolution; simian arterivirus; simian hemorrhagic fever virus; virology; within-host diversity