Simian T lymphotropic virus 1 Infection of Papio anubis: Tax sequence heterogeneity and T cell recognition

James M. Termini, Diogo M. Magnani, Helen S. Maxwell, William Lauer, Iris Castro, Jerilyn Pecotte, Glen N Barber, David Watkins, Ronald Charles Desrosiers

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Abstract

Baboons naturally infected with simian T lymphotropic virus (STLV) are a potentially useful model system for the study of vaccination against human T lymphotropic virus (HTLV). Here we expanded the number of available full-length baboon STLV-1 sequences from one to three and related the T cell responses that recognize the immunodominant Tax protein to the tax sequences present in two individual baboons. Continuously growing T cell lines were established from two baboons, animals 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these T cell lines revealed them to be closely related but distinct from each other and from the baboon STLV-1 sequence in the NCBI sequence database. Overlapping peptides corresponding to each unique Tax sequence and to the reference baboon Tax sequence were used to analyze recognition by T cells from each baboon using intracellular cytokine staining (ICS). Individual baboons expressed more gamma interferon and tumor necrosis factor alpha in response to Tax peptides corresponding to their own STLV-1 sequence than in response to Tax peptides corresponding to the reference baboon STLV-1 sequence. Thus, our analyses revealed distinct but closely related STLV-1 genome sequences in two baboons, extremely low heterogeneity of STLV sequences within each baboon, no evidence for superinfection within each baboon, and a ready ability of T cells in each baboon to recognize circulating Tax sequences. While amino acid substitutions that result in escape from CD8+ T cell recognition were not observed, premature stop codons were observed in 7% and 56% of tax sequences from peripheral blood mononuclear cells from animals 12141 and 12752, respectively.

Original languageEnglish (US)
Article numbere00950-17
JournalJournal of Virology
Volume91
Issue number20
DOIs
StatePublished - Oct 1 2017

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Keywords

  • Intracellular cytokine staining
  • Next generation sequencing
  • Papio anubis
  • Simian T-cell leukemia virus
  • Tax

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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