Adoptive transfer of engineered rhesus simian immunodeficiency virus-specific CD8+ T cells reduces the number of transmitted/founder viruses established in rhesus macaques

Victor I. Ayala, Matthew T. Trivett, Eugene V. Barsov, Sumiti Jain, Michael Piatak, Charles M. Trubey, W. Gregory Alvord, Elena Chertova, James D. Roser, Jeremy Smedley, Alexander Komin, Brandon F. Keele, Claes Ohlen, David E. Ott

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

AIDS virus infections are rarely controlled by cell-mediated immunity, in part due to viral immune evasion and immunodeficiency resulting from CD4+ T-cell infection. One likely aspect of this failure is that antiviral cellular immune responses are either absent or present at low levels during the initial establishment of infection. To test whether an extensive, timely, and effective response could reduce the establishment of infection from a high-dose inoculum, we adoptively transferred large numbers of T cells that were molecularly engineered with anti-simian immunodeficiency virus (anti-SIV) activity into rhesus macaques 3 days following an intrarectal SIV inoculation. To measure in vivo antiviral activity, we assessed the number of viruses transmitted using SIVmac239X, a molecularly tagged viral stock containing 10 genotypic variants, at a dose calculated to transmit 12 founder viruses. Single-genome sequencing of plasma virus revealed that the two animals receiving T cells expressing SIV-specific T-cell receptors (TCRs) had significantly fewer viral genotypes than the two control animals receiving non-SIV-specific T cells (means of 4.0 versus 7.5 transmitted viral genotypes; P = 0.044). Accounting for the likelihood of transmission of multiple viruses of a particular genotype, the calculated means of the total number of founder viruses transmitted were 4.5 and 14.5 in the experimental and control groups, respectively (P = 0.021). Thus, a large antiviral T-cell response timed with virus exposure can limit viral transmission. The presence of strong, preexisting T-cell responses, including those induced by vaccines, might help prevent the establishment of infection at the lower-exposure doses in humans that typically transmit only a single virus.

Original languageEnglish (US)
Pages (from-to)9942-9952
Number of pages11
JournalJournal of Virology
Volume90
Issue number21
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Adoptive Transfer
Macaca mulatta
T-lymphocytes
Cell Count
Viruses
T-Lymphocytes
viruses
Antiviral Agents
Genotype
infection
Infection
Cellular Immunity
cell-mediated immunity
genotype
dosage
Immune Evasion
immune evasion
Virus Diseases

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Adoptive transfer of engineered rhesus simian immunodeficiency virus-specific CD8+ T cells reduces the number of transmitted/founder viruses established in rhesus macaques. / Ayala, Victor I.; Trivett, Matthew T.; Barsov, Eugene V.; Jain, Sumiti; Piatak, Michael; Trubey, Charles M.; Alvord, W. Gregory; Chertova, Elena; Roser, James D.; Smedley, Jeremy; Komin, Alexander; Keele, Brandon F.; Ohlen, Claes; Ott, David E.

In: Journal of Virology, Vol. 90, No. 21, 01.01.2016, p. 9942-9952.

Research output: Contribution to journalArticle

Ayala, VI, Trivett, MT, Barsov, EV, Jain, S, Piatak, M, Trubey, CM, Alvord, WG, Chertova, E, Roser, JD, Smedley, J, Komin, A, Keele, BF, Ohlen, C & Ott, DE 2016, 'Adoptive transfer of engineered rhesus simian immunodeficiency virus-specific CD8+ T cells reduces the number of transmitted/founder viruses established in rhesus macaques', Journal of Virology, vol. 90, no. 21, pp. 9942-9952. https://doi.org/10.1128/JVI.01522-16
Ayala, Victor I. ; Trivett, Matthew T. ; Barsov, Eugene V. ; Jain, Sumiti ; Piatak, Michael ; Trubey, Charles M. ; Alvord, W. Gregory ; Chertova, Elena ; Roser, James D. ; Smedley, Jeremy ; Komin, Alexander ; Keele, Brandon F. ; Ohlen, Claes ; Ott, David E. / Adoptive transfer of engineered rhesus simian immunodeficiency virus-specific CD8+ T cells reduces the number of transmitted/founder viruses established in rhesus macaques. In: Journal of Virology. 2016 ; Vol. 90, No. 21. pp. 9942-9952.
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abstract = "AIDS virus infections are rarely controlled by cell-mediated immunity, in part due to viral immune evasion and immunodeficiency resulting from CD4+ T-cell infection. One likely aspect of this failure is that antiviral cellular immune responses are either absent or present at low levels during the initial establishment of infection. To test whether an extensive, timely, and effective response could reduce the establishment of infection from a high-dose inoculum, we adoptively transferred large numbers of T cells that were molecularly engineered with anti-simian immunodeficiency virus (anti-SIV) activity into rhesus macaques 3 days following an intrarectal SIV inoculation. To measure in vivo antiviral activity, we assessed the number of viruses transmitted using SIVmac239X, a molecularly tagged viral stock containing 10 genotypic variants, at a dose calculated to transmit 12 founder viruses. Single-genome sequencing of plasma virus revealed that the two animals receiving T cells expressing SIV-specific T-cell receptors (TCRs) had significantly fewer viral genotypes than the two control animals receiving non-SIV-specific T cells (means of 4.0 versus 7.5 transmitted viral genotypes; P = 0.044). Accounting for the likelihood of transmission of multiple viruses of a particular genotype, the calculated means of the total number of founder viruses transmitted were 4.5 and 14.5 in the experimental and control groups, respectively (P = 0.021). Thus, a large antiviral T-cell response timed with virus exposure can limit viral transmission. The presence of strong, preexisting T-cell responses, including those induced by vaccines, might help prevent the establishment of infection at the lower-exposure doses in humans that typically transmit only a single virus.",
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AU - Barsov, Eugene V.

AU - Jain, Sumiti

AU - Piatak, Michael

AU - Trubey, Charles M.

AU - Alvord, W. Gregory

AU - Chertova, Elena

AU - Roser, James D.

AU - Smedley, Jeremy

AU - Komin, Alexander

AU - Keele, Brandon F.

AU - Ohlen, Claes

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N2 - AIDS virus infections are rarely controlled by cell-mediated immunity, in part due to viral immune evasion and immunodeficiency resulting from CD4+ T-cell infection. One likely aspect of this failure is that antiviral cellular immune responses are either absent or present at low levels during the initial establishment of infection. To test whether an extensive, timely, and effective response could reduce the establishment of infection from a high-dose inoculum, we adoptively transferred large numbers of T cells that were molecularly engineered with anti-simian immunodeficiency virus (anti-SIV) activity into rhesus macaques 3 days following an intrarectal SIV inoculation. To measure in vivo antiviral activity, we assessed the number of viruses transmitted using SIVmac239X, a molecularly tagged viral stock containing 10 genotypic variants, at a dose calculated to transmit 12 founder viruses. Single-genome sequencing of plasma virus revealed that the two animals receiving T cells expressing SIV-specific T-cell receptors (TCRs) had significantly fewer viral genotypes than the two control animals receiving non-SIV-specific T cells (means of 4.0 versus 7.5 transmitted viral genotypes; P = 0.044). Accounting for the likelihood of transmission of multiple viruses of a particular genotype, the calculated means of the total number of founder viruses transmitted were 4.5 and 14.5 in the experimental and control groups, respectively (P = 0.021). Thus, a large antiviral T-cell response timed with virus exposure can limit viral transmission. The presence of strong, preexisting T-cell responses, including those induced by vaccines, might help prevent the establishment of infection at the lower-exposure doses in humans that typically transmit only a single virus.

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