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 LiMichael Piatak, Jeffrey D. Lifson, Brandon F. Keele, Patricia N. Fultz, Andrew A. Lackner, James A. Hoxie

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 <15 to 50 RNA copies/ml. CD4+ 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

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this