Elite control, gut CD4 T cell sparing, and enhanced mucosal T cell responses in Macaca nemestrina infected by a simian immunodeficiency virus lacking a gp41 trafficking motif

Matthew W. Breed, Samra E. Elser, Workineh Torben, Andrea P O Jordan, Pyone P. Aye, Cecily Midkiff, Faith Schiro, Chie Sugimoto, Xavier Alvarez-Hernandez, Robert V. Blair, Anoma Somasunderam, Netanya S. Utay, Marcelo J. Kuroda, Bapi Pahar, Roger W. Wiseman, David H. O'Connor, Celia C. LaBranche, David C. Montefiori, Mark Marsh, Yuan Li & 6 others Michael Piatak, Jeffrey D. Lifson, Brandon F. Keele, Patricia N. Fultz, Andrew A. Lackner, James A. Hoxie

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Deletion of Gly-720 and Tyr-721 from a highly conserved GYxxØ trafficking signal in the SIVmac239 envelope glycoprotein cytoplasmic domain, producing a virus termed ΔGY, leads to a striking perturbation in pathogenesis in rhesus macaques (Macaca mulatta). Infected macaques develop immune activation and progress to AIDS, but with only limited and transient infection of intestinal CD4+ T cells and an absence of microbial translocation. Here we evaluated ΔGY in pig-tailed macaques (Macaca nemestrina), a species in which SIVmac239 infection typically leads to increased immune activation and more rapid progression to AIDS than in rhesus macaques. In pig-tailed macaques, ΔGY also replicated acutely to high peak plasma RNA levels identical to those for SIVmac239 and caused only transient infection of CD4+ T cells in the gut lamina propria and no microbial translocation. However, in marked contrast to rhesus macaques, 19 of 21 pig-tailed macaques controlled ΔGY replication with plasma viral loads of + T cells were preserved in blood and gut for up to 100 weeks with no immune activation or disease progression. Robust antiviral CD4+ T cell responses were seen, particularly in the gut. Anti-CD8 antibody depletion demonstrated CD8+ cellular control of viral replication. Two pig-tailed macaques progressed to disease with persisting viremia and possible compensatory mutations in the cytoplasmic tail. These studies demonstrate a marked perturbation in pathogenesis caused by ΔGY's ablation of the GYxxØ trafficking motif and reveal, paradoxically, that viral control is enhanced in a macaque species typically predisposed to more pathogenic manifestations of simian immunodeficiency virus (SIV) infection.

Original languageEnglish (US)
Pages (from-to)10156-10175
Number of pages20
JournalJournal of Virology
Volume89
Issue number20
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Macaca nemestrina
Simian immunodeficiency virus
Simian Immunodeficiency Virus
Macaca
Macaca mulatta
digestive system
T-lymphocytes
T-Lymphocytes
Swine
infection
pathogenesis
Acquired Immunodeficiency Syndrome
Infection
viremia
laminae (animals)
virus replication
viral load
disease course
Viremia
Virus Diseases

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Elite control, gut CD4 T cell sparing, and enhanced mucosal T cell responses in Macaca nemestrina infected by a simian immunodeficiency virus lacking a gp41 trafficking motif. / Breed, Matthew W.; Elser, Samra E.; Torben, Workineh; Jordan, Andrea P O; Aye, Pyone P.; Midkiff, Cecily; Schiro, Faith; Sugimoto, Chie; Alvarez-Hernandez, Xavier; Blair, Robert V.; Somasunderam, Anoma; Utay, Netanya S.; Kuroda, Marcelo J.; Pahar, Bapi; Wiseman, Roger W.; O'Connor, David H.; LaBranche, Celia C.; Montefiori, David C.; Marsh, Mark; Li, Yuan; Piatak, Michael; Lifson, Jeffrey D.; Keele, Brandon F.; Fultz, Patricia N.; Lackner, Andrew A.; Hoxie, James A.

In: Journal of Virology, Vol. 89, No. 20, 2015, p. 10156-10175.

Research output: Contribution to journalArticle

Breed, MW, Elser, SE, Torben, W, Jordan, APO, Aye, PP, Midkiff, C, Schiro, F, Sugimoto, C, Alvarez-Hernandez, X, Blair, RV, Somasunderam, A, Utay, NS, Kuroda, MJ, Pahar, B, Wiseman, RW, O'Connor, DH, LaBranche, CC, Montefiori, DC, Marsh, M, Li, Y, Piatak, M, Lifson, JD, Keele, BF, Fultz, PN, Lackner, AA & Hoxie, JA 2015, 'Elite control, gut CD4 T cell sparing, and enhanced mucosal T cell responses in Macaca nemestrina infected by a simian immunodeficiency virus lacking a gp41 trafficking motif', Journal of Virology, vol. 89, no. 20, pp. 10156-10175. https://doi.org/10.1128/JVI.01134-15
Breed, Matthew W. ; Elser, Samra E. ; Torben, Workineh ; Jordan, Andrea P O ; Aye, Pyone P. ; Midkiff, Cecily ; Schiro, Faith ; Sugimoto, Chie ; Alvarez-Hernandez, Xavier ; Blair, Robert V. ; Somasunderam, Anoma ; Utay, Netanya S. ; Kuroda, Marcelo J. ; Pahar, Bapi ; Wiseman, Roger W. ; O'Connor, David H. ; LaBranche, Celia C. ; Montefiori, David C. ; Marsh, Mark ; Li, Yuan ; Piatak, Michael ; Lifson, Jeffrey D. ; Keele, Brandon F. ; Fultz, Patricia N. ; Lackner, Andrew A. ; Hoxie, James A. / Elite control, gut CD4 T cell sparing, and enhanced mucosal T cell responses in Macaca nemestrina infected by a simian immunodeficiency virus lacking a gp41 trafficking motif. In: Journal of Virology. 2015 ; Vol. 89, No. 20. pp. 10156-10175.
@article{85c3efe089a1405d993eecb92474524b,
title = "Elite control, gut CD4 T cell sparing, and enhanced mucosal T cell responses in Macaca nemestrina infected by a simian immunodeficiency virus lacking a gp41 trafficking motif",
abstract = "Deletion of Gly-720 and Tyr-721 from a highly conserved GYxx{\O} trafficking signal in the SIVmac239 envelope glycoprotein cytoplasmic domain, producing a virus termed ΔGY, leads to a striking perturbation in pathogenesis in rhesus macaques (Macaca mulatta). Infected macaques develop immune activation and progress to AIDS, but with only limited and transient infection of intestinal CD4+ T cells and an absence of microbial translocation. Here we evaluated ΔGY in pig-tailed macaques (Macaca nemestrina), a species in which SIVmac239 infection typically leads to increased immune activation and more rapid progression to AIDS than in rhesus macaques. In pig-tailed macaques, ΔGY also replicated acutely to high peak plasma RNA levels identical to those for SIVmac239 and caused only transient infection of CD4+ T cells in the gut lamina propria and no microbial translocation. However, in marked contrast to rhesus macaques, 19 of 21 pig-tailed macaques controlled ΔGY replication with plasma viral loads of + T cells were preserved in blood and gut for up to 100 weeks with no immune activation or disease progression. Robust antiviral CD4+ T cell responses were seen, particularly in the gut. Anti-CD8 antibody depletion demonstrated CD8+ cellular control of viral replication. Two pig-tailed macaques progressed to disease with persisting viremia and possible compensatory mutations in the cytoplasmic tail. These studies demonstrate a marked perturbation in pathogenesis caused by ΔGY's ablation of the GYxx{\O} trafficking motif and reveal, paradoxically, that viral control is enhanced in a macaque species typically predisposed to more pathogenic manifestations of simian immunodeficiency virus (SIV) infection.",
author = "Breed, {Matthew W.} and Elser, {Samra E.} and Workineh Torben and Jordan, {Andrea P O} and Aye, {Pyone P.} and Cecily Midkiff and Faith Schiro and Chie Sugimoto and Xavier Alvarez-Hernandez and Blair, {Robert V.} and Anoma Somasunderam and Utay, {Netanya S.} and Kuroda, {Marcelo J.} and Bapi Pahar and Wiseman, {Roger W.} and O'Connor, {David H.} and LaBranche, {Celia C.} and Montefiori, {David C.} and Mark Marsh and Yuan Li and Michael Piatak and Lifson, {Jeffrey D.} and Keele, {Brandon F.} and Fultz, {Patricia N.} and Lackner, {Andrew A.} and Hoxie, {James A.}",
year = "2015",
doi = "10.1128/JVI.01134-15",
language = "English (US)",
volume = "89",
pages = "10156--10175",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "20",

}

TY - JOUR

T1 - Elite control, gut CD4 T cell sparing, and enhanced mucosal T cell responses in Macaca nemestrina infected by a simian immunodeficiency virus lacking a gp41 trafficking motif

AU - Breed, Matthew W.

AU - Elser, Samra E.

AU - Torben, Workineh

AU - Jordan, Andrea P O

AU - Aye, Pyone P.

AU - Midkiff, Cecily

AU - Schiro, Faith

AU - Sugimoto, Chie

AU - Alvarez-Hernandez, Xavier

AU - Blair, Robert V.

AU - Somasunderam, Anoma

AU - Utay, Netanya S.

AU - Kuroda, Marcelo J.

AU - Pahar, Bapi

AU - Wiseman, Roger W.

AU - O'Connor, David H.

AU - LaBranche, Celia C.

AU - Montefiori, David C.

AU - Marsh, Mark

AU - Li, Yuan

AU - Piatak, Michael

AU - Lifson, Jeffrey D.

AU - Keele, Brandon F.

AU - Fultz, Patricia N.

AU - Lackner, Andrew A.

AU - Hoxie, James A.

PY - 2015

Y1 - 2015

N2 - Deletion of Gly-720 and Tyr-721 from a highly conserved GYxxØ trafficking signal in the SIVmac239 envelope glycoprotein cytoplasmic domain, producing a virus termed ΔGY, leads to a striking perturbation in pathogenesis in rhesus macaques (Macaca mulatta). Infected macaques develop immune activation and progress to AIDS, but with only limited and transient infection of intestinal CD4+ T cells and an absence of microbial translocation. Here we evaluated ΔGY in pig-tailed macaques (Macaca nemestrina), a species in which SIVmac239 infection typically leads to increased immune activation and more rapid progression to AIDS than in rhesus macaques. In pig-tailed macaques, ΔGY also replicated acutely to high peak plasma RNA levels identical to those for SIVmac239 and caused only transient infection of CD4+ T cells in the gut lamina propria and no microbial translocation. However, in marked contrast to rhesus macaques, 19 of 21 pig-tailed macaques controlled ΔGY replication with plasma viral loads of + T cells were preserved in blood and gut for up to 100 weeks with no immune activation or disease progression. Robust antiviral CD4+ T cell responses were seen, particularly in the gut. Anti-CD8 antibody depletion demonstrated CD8+ cellular control of viral replication. Two pig-tailed macaques progressed to disease with persisting viremia and possible compensatory mutations in the cytoplasmic tail. These studies demonstrate a marked perturbation in pathogenesis caused by ΔGY's ablation of the GYxxØ trafficking motif and reveal, paradoxically, that viral control is enhanced in a macaque species typically predisposed to more pathogenic manifestations of simian immunodeficiency virus (SIV) infection.

AB - Deletion of Gly-720 and Tyr-721 from a highly conserved GYxxØ trafficking signal in the SIVmac239 envelope glycoprotein cytoplasmic domain, producing a virus termed ΔGY, leads to a striking perturbation in pathogenesis in rhesus macaques (Macaca mulatta). Infected macaques develop immune activation and progress to AIDS, but with only limited and transient infection of intestinal CD4+ T cells and an absence of microbial translocation. Here we evaluated ΔGY in pig-tailed macaques (Macaca nemestrina), a species in which SIVmac239 infection typically leads to increased immune activation and more rapid progression to AIDS than in rhesus macaques. In pig-tailed macaques, ΔGY also replicated acutely to high peak plasma RNA levels identical to those for SIVmac239 and caused only transient infection of CD4+ T cells in the gut lamina propria and no microbial translocation. However, in marked contrast to rhesus macaques, 19 of 21 pig-tailed macaques controlled ΔGY replication with plasma viral loads of + T cells were preserved in blood and gut for up to 100 weeks with no immune activation or disease progression. Robust antiviral CD4+ T cell responses were seen, particularly in the gut. Anti-CD8 antibody depletion demonstrated CD8+ cellular control of viral replication. Two pig-tailed macaques progressed to disease with persisting viremia and possible compensatory mutations in the cytoplasmic tail. These studies demonstrate a marked perturbation in pathogenesis caused by ΔGY's ablation of the GYxxØ trafficking motif and reveal, paradoxically, that viral control is enhanced in a macaque species typically predisposed to more pathogenic manifestations of simian immunodeficiency virus (SIV) infection.

UR - http://www.scopus.com/inward/record.url?scp=84942163383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942163383&partnerID=8YFLogxK

U2 - 10.1128/JVI.01134-15

DO - 10.1128/JVI.01134-15

M3 - Article

VL - 89

SP - 10156

EP - 10175

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 20

ER -