Identification and spontaneous immune targeting of an endogenous retrovirus K envelope protein in the Indian rhesus macaque model of human disease

Helen L. Wu, Enrique J. Léon, Lyle T. Wallace, Francesca A. Nimiyongskul, Matthew B. Buechler, Laura P. Newman, Philip A. Castrovinci, R. Paul Johnson, Robert J. Gifford, R. Brad Jones, Jonah Sacha

Research output: Contribution to journalArticle

4 Citations (Scopus)

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. Findings: 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.

Original languageEnglish (US)
JournalRetrovirology
DOIs
StateAccepted/In press - Jan 15 2016

Fingerprint

Endogenous Retroviruses
Macaca mulatta
Macaca
Primates
Simian Retroviruses
protein K
Chromosomes, Human, Pair 12
Forensic Anthropology
Messenger RNA
Fossils
Sequence Deletion
Adaptive Immunity
Viral Proteins
Human Genome
Pathologic Processes
Humoral Immunity
Human Activities
Germ Cells
Cellular Immunity
Virion

Keywords

  • Antibodies
  • Endogenous retroviruses (ERVs)
  • Env proteins
  • Simian immunodeficiency virus (SIV)
  • T cells

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Identification and spontaneous immune targeting of an endogenous retrovirus K envelope protein in the Indian rhesus macaque model of human disease. / Wu, Helen L.; Léon, Enrique J.; Wallace, Lyle T.; Nimiyongskul, Francesca A.; Buechler, Matthew B.; Newman, Laura P.; Castrovinci, Philip A.; Paul Johnson, R.; Gifford, Robert J.; Brad Jones, R.; Sacha, Jonah.

In: Retrovirology, 15.01.2016.

Research output: Contribution to journalArticle

Wu, HL, Léon, EJ, Wallace, LT, Nimiyongskul, FA, Buechler, MB, Newman, LP, Castrovinci, PA, Paul Johnson, R, Gifford, RJ, Brad Jones, R & Sacha, J 2016, 'Identification and spontaneous immune targeting of an endogenous retrovirus K envelope protein in the Indian rhesus macaque model of human disease', Retrovirology. https://doi.org/10.1186/s12977-016-0238-0
Wu, Helen L. ; Léon, Enrique J. ; Wallace, Lyle T. ; Nimiyongskul, Francesca A. ; Buechler, Matthew B. ; Newman, Laura P. ; Castrovinci, Philip A. ; Paul Johnson, R. ; Gifford, Robert J. ; Brad Jones, R. ; Sacha, Jonah. / Identification and spontaneous immune targeting of an endogenous retrovirus K envelope protein in the Indian rhesus macaque model of human disease. In: Retrovirology. 2016.
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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. Findings: 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.",
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AU - Buechler, Matthew B.

AU - Newman, Laura P.

AU - Castrovinci, Philip A.

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AU - Gifford, Robert J.

AU - Brad Jones, R.

AU - Sacha, Jonah

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AB - 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. Findings: 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.

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