title: Identification and spontaneous immune targeting of an endogenous retrovirus K envelope protein in the Indian rhesus macaque model of human disease.
abstract: BACKGROUND
  Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that have invaded the germ line of both humans and non-human primates. Most ERVs are functionally crippled by deletions, mutations, and hypermethylation, leading to the view that they are inert genomic fossils. However, some ERVs can produce mRNA transcripts, functional viral proteins, and even non-infectious virus particles during certain developmental and pathological processes. While there have been reports of ERV-specific immunity associated with ERV activity in humans, adaptive immune responses to ERV-encoded gene products remain poorly defined and have not been investigated in the physiologically relevant non-human primate model of human disease.
  
  
  RESULTS
  Here, we identified the rhesus macaque equivalent of the biologically active human ERV-K (HML-2), simian ERV-K (SERV-K1), which retains intact open reading frames for both Gag and Env on chromosome 12 in the macaque genome. From macaque cells we isolated a spliced mRNA product encoding SERV-K1 Env, which possesses all the structural features of a canonical, functional retroviral Envelope protein. Furthermore, we identified rare, but robust T cell responses as well as frequent antibody responses targeting SERV-K1 Env in rhesus macaques.
  
  
  CONCLUSIONS
  These data demonstrate that SERV-K1 retains biological activity sufficient to induce cellular and humoral immune responses in rhesus macaques. As ERV-K is the youngest and most active ERV family in the human genome, the identification and characterization of the simian orthologue in rhesus macaques provides a highly relevant animal model in which to study the role of ERV-K in developmental and disease states.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, USA. wuhe@ohsu.edu.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Wu
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, USA. leonen@ohsu.edu.|Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR, 97007, USA. leonen@ohsu.edu.
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Léon
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA. wallacly@onid.oregonstate.edu.
authors.forename: Lyle T
authors.initials: LT
authors.lastname: Wallace
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA. franimit@gmail.com.
authors.forename: Francesca A
authors.initials: FA
authors.lastname: Nimiyongskul
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA. matthew.buechler@gmail.com.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Buechler
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA. lauranewman@gmail.com.
authors.forename: Laura P
authors.initials: LP
authors.lastname: Newman
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA. castrovinci@primate.wisc.edu.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Castrovinci
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA. rpaul.johnson@emory.edu.
authors.forename: R
authors.initials: R
authors.lastname: Paul Johnson
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, UK. robert.gifford@glasgow.ac.uk.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gifford
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington DC, USA. bradjones@email.gwu.edu.
authors.forename: R
authors.initials: R
authors.lastname: Brad Jones
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, USA. sacha@ohsu.edu.|Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR, 97007, USA. sacha@ohsu.edu.
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015686:Gene Products, env