Cellular Immune Responses against Simian T-Lymphotropic Virus Type 1 Target Tax in Infected Baboons

Castro, Iris; Giret, Teresa M.; Magnani, Diogo M.; Maxwell, Helen S.; Umland, Oliver; Perry, Jessica K.; Pecotte, Jerilyn; Brasky, Kathleen M.; Barber, Glen N.; Desrosiers, Ronald C.; Watkins, David I.

doi:10.1128/jvi.00281-16

Cited by 9 publications

(16 citation statements)

References 76 publications

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“…Although the polymorphisms observed in animals 12141 and 12752 appeared to be located in regions of Tax identified by Castro et al (17) to be epitopes of CD8 ϩ T cell recognition, we found that T cells from both animals recognized both the reference peptide and the variant peptide at reasonably high frequencies. The correspondence of sequence polymorphisms within the targets of CD8 ϩ T cell recognition suggests the possibility of immune selective pressure.…”

Section: Discussioncontrasting

confidence: 54%

“…Previous studies in humans have observed that immunodominant responses are directed to the Tax protein (18)(19)(20)23). In a recently published study, immunogenic regions of Tax were mapped in individual animals using peptides that correspond to those of the reference genome from isolate F88395 (17). Here, we set out to determine the influence of sequence polymorphisms on recognition of virus by CD8 ϩ T cells from each of the two baboons in our study.…”

Section: Resultsmentioning

confidence: 99%

“…Here, we set out to determine the influence of sequence polymorphisms on recognition of virus by CD8 ϩ T cells from each of the two baboons in our study. During our preliminary analysis, it appeared that regions with sequence polymorphisms tended to be regions identified by Castro et al to be immunogenic regions of Tax (17). To examine whether these sequence polymorphisms could represent immune escape variants, we constructed variant peptides, which are described in Table 3.…”

Section: Resultsmentioning

confidence: 99%

“…As a negative control, PBMC from an STLV-1-negative animal (animal 15659) were included. Because animal 12869 has a well-documented CD8 ϩ T cell response to Tax (17), PBMC from this animal were included as a positive control.…”

Section: Resultsmentioning

confidence: 99%

“…Due to the high frequencies of STLV-1 infection in both wild and captive baboons, we propose that baboons are a potentially useful model system for such studies. A recent study analyzed the cellular immune response to STLV-1 in infected olive baboons (Papio anubis) (17). This study utilized peptides based on a baboon SLTV-1 reference sequence found in the NCBI database.…”

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confidence: 99%

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

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Magnani

Maxwell

et al. 2017

J Virol

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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.

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Section: Discussioncontrasting

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Termini

Magnani

Maxwell

et al. 2017

J Virol

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Whole body clonality analysis in an aggressive STLV-1 associated leukemia (ATLL) reveals an unexpected clonal complexity

et al. 2017

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HTLV-1 causes Adult T cell Leukemia/Lymphoma (ATLL) in humans. We describe an ATL-like disease in a 9 year-old female baboon naturally infected with STLV-1 (the simian counterpart of HTLV-1), with a lymphocyte count over 1010/L, lymphocytes with abnormal nuclear morphology, and pulmonary and skin lesions. The animal was treated with a combination of AZT and alpha interferon. Proviral load (PVL) was measured every week. Because the disease continued to progress, the animal was euthanized. Abnormal infiltrates of CD3+CD25+ lymphocytes and Tax-positive cells were found by histological analyses in both lymphoid and non-lymphoid organs. PVL was measured and clonal diversity was assessed by LM-PCR (Ligation-Mediated Polymerase Chain Reaction) and high throughput sequencing, in blood during treatment and in 14 different organs. The highest PVL was found in lymph nodes, spleen and lungs. One major clone and a number of intermediate abundance clones were present in blood throughout the course of treatment, and in organs. These results represent the first multi-organ clonality study in ATLL. We demonstrate a previously undescribed clonal complexity in ATLL. Our data reinforce the usefulness of natural STLV-1 infection as a model of ATLL

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Fifty‐one full‐length major histocompatibility complex class II alleles in the olive baboon (Papio anubis)

Otting

Wiel

Doxiadis

et al. 2016

HLA

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Cellular Immune Responses against Simian T-Lymphotropic Virus Type 1 Target Tax in Infected Baboons

Cited by 9 publications

References 76 publications

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

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

Whole body clonality analysis in an aggressive STLV-1 associated leukemia (ATLL) reveals an unexpected clonal complexity

Fifty‐one full‐length major histocompatibility complex class II alleles in the olive baboon (Papio anubis)

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