Simian T Lymphotropic Virus 1 Infection of Papio anubis:taxSequence Heterogeneity and T Cell Recognition

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 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 sequences from peripheral blood mononuclear cells from animals 12141 and 12752, respectively. 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 preventive vaccine would significantly impact the global burden associated with HTLV infections. Here we provide fundamental information on the simian T lymphotropic virus (STLV) 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 of truncated variants in the major target of cellular immune responses all parallel what are seen with HTLV infection of humans. These results justify the use of STLV-infected baboons as a model system for vaccine development efforts.

STLV-1 co-infection is correlated with an increased SFV proviral load in the peripheral blood of SFV/STLV-1 naturally infected non-human primates

“…It is also transmitted to humans after bites [ 8 ]. STLV-1 and HTLV-1 strains from the same regions are usually almost undistinguishable at the nucleotide level and more than thirty Old World NHP species, including baboons, are infected with STLV-1 [ 9 – 13 ]. Even if STLV-1 has been infecting NHPs for millennia [ 14 ], it still causes lymphoproliferative diseases in naturally infected NHPs (i.e.…”

A Review on Zoonotic Pathogens Associated with Non-Human Primates: Understanding the Potential Threats to Humans

“…Interestingly, Mra18C9 lacks three auxiliary open reading frames; therefore, to determine whether deletion of the auxiliary protein is specific to this strain, the complete STLV-1 genome available from GenBank was analyzed. The results showed STLV-1 commonly lacks one or multiple secondary open reading frames [ 60 ]. Akari et al suggested that frequent horizontal and mother-to-child transmission contributes to the high prevalence of STLV-1 infection in Japanese macaques [ 59 ].…”

STLV-1 as a model for studying HTLV-1 infection

“…Given well-established results published in the HTLV-1 situation, this is likely due to STLV-1 Tax expression, although this hypothesis has not been formally demonstrated. IL-2 and IFNγ results were also obtained in asymptomatic STLV-1-positive Macaca mulatta [87], while anti IFNγ and TNF-α responses against Tax expressing cells were also observed in STLV-1 infected baboons [85]. STLV-1 infection also promotes CTL response against STLV-1 Tax protein [84, 85].…”