Glycosylation of simian immunodeficiency virus influences immune-tissue targeting during primary infection, leading to immunodeficiency or viral control

Chie Sugimoto, Shinichiro Nakamura, Shoko I. Hagen, Yasuko Tsunetsugu-Yokota, Francois Villinger, Aftab A. Ansari, Yasuo Suzuki, Naoki Yamamoto, Yoshiyuki Nagai, Louis Picker, Kazuyasu Mori

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Glycans of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) play pivotal roles in modulating virus-target cell interactions. We have previously reported that, whereas SIVmac239 is pathogenic, its deglycosylated essentially nonpathogenic mutant (Δ5G) serves as a live-attenuated vaccine, although both replicate similarly during primary infection. These findings prompted us to determine whether such a polarized clinical outcome was due to differences in the immune tissues targeted by these viruses, where functionally and phenotypically different memory CD4+ T cells reside. The results showed that Δ5G replicates in secondary lymphoid tissue (SLT) at 1- to 2-log-lower levels than SIVmac239, whereas SIVmac239-infected but not Δ5G-infected animals deplete CXCR3+ CCR5+ transitional memory (TrM) CD4+ T cells. An early robust Δ5G replication was localized to small intestinal tissue, especially the lamina propria (effector site) rather than isolated lymphoid follicles (inductive site) and was associated with the induction and depletion of CCR6+ CXCR3- CCR5+ effector memory CD4+ T cells. These results suggest that differential glycosylation of Env dictates the type of tissue-resident CD4+ T cells that are targeted, which leads to pathogenic infection of TrM-Th1 cells in SLT and nonpathogenic infection of Th17 cells in the small intestine, respectively.

Original languageEnglish (US)
Pages (from-to)9323-9336
Number of pages14
JournalJournal of Virology
Volume86
Issue number17
DOIs
Publication statusPublished - Sep 2012

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ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Sugimoto, C., Nakamura, S., Hagen, S. I., Tsunetsugu-Yokota, Y., Villinger, F., Ansari, A. A., ... Mori, K. (2012). Glycosylation of simian immunodeficiency virus influences immune-tissue targeting during primary infection, leading to immunodeficiency or viral control. Journal of Virology, 86(17), 9323-9336. https://doi.org/10.1128/JVI.00948-12