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

Natural infection of baboons with simian T lymphotropic virus (STLV) is a potentially useful model system for study of vaccination against the human virus HTLV. Here we expand the number of available full-length STLV-1 baboon sequences from one to three and relate 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, 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these lines revealed them to be closely related but distinct from each other and from the STLV-1 baboon 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 IFN-γ and TNF-α in response to Tax peptides corresponding to their own sequence than with Tax peptides corresponding to the reference baboon 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 only in tax sequences obtained from PBMC at 7% in 12141 and 56% in 12752.Importance: It has been estimated that approximately 100,000 people suffer serious morbidity and 10,000 people die each year from the consequences associated with human T lymphotropic virus (HTLV) infection. There are no antiviral drugs and no preventive vaccine. A preventative vaccine would significantly impact the global burden associated with HTLV infections. Here we provide fundamental information on the simian T lymphotropic virus (STLV) being naturally transmitted in a colony of captive baboons. The limited viral sequence heterogeneity in individual baboons, the identity of the viral gene product that is the major target of cellular immune responses, the persistence of viral amino acid sequences that are the major targets of cellular immune responses, and the emergence in vivo of truncated variants in the major target of cellular immune responses all parallel what is seen with HTLV infection of humans. These results justify the use of STLV-baboon model systems for vaccine development efforts.