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 language | English (US) |
|---|---|
| Article number | e00950-17 |
| Journal | Journal of Virology |
| Volume | 91 |
| Issue number | 20 |
| DOIs | |
| State | Published - 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
Cite this
Simian T lymphotropic virus 1 Infection of Papio anubis : Tax sequence heterogeneity and T cell recognition. / Termini, James M.; Magnani, Diogo M.; Maxwell, Helen S.; Lauer, William; Castro, Iris; Pecotte, Jerilyn; Barber, Glen N; Watkins, David; Desrosiers, Ronald Charles.
In: Journal of Virology, Vol. 91, No. 20, e00950-17, 01.10.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Simian T lymphotropic virus 1 Infection of Papio anubis
T2 - Tax sequence heterogeneity and T cell recognition
AU - Termini, James M.
AU - Magnani, Diogo M.
AU - Maxwell, Helen S.
AU - Lauer, William
AU - Castro, Iris
AU - Pecotte, Jerilyn
AU - Barber, Glen N
AU - Watkins, David
AU - Desrosiers, Ronald Charles
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - Intracellular cytokine staining
KW - Next generation sequencing
KW - Papio anubis
KW - Simian T-cell leukemia virus
KW - Tax
UR - http://www.scopus.com/inward/record.url?scp=85030117801&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030117801&partnerID=8YFLogxK
U2 - 10.1128/JVI.00950-17
DO - 10.1128/JVI.00950-17
M3 - Article
VL - 91
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 20
M1 - e00950-17
ER -