Glycosylation of Simian Immunodeficiency Virus Influences Immune-Tissue Targeting during Primary Infection, Leading to Immunodeficiency or Viral Control

• Type of Material: Article
• Authors: Chie Sugimoto, Japan Science and Technology Agency; Shinichiro Nakamura, Shiga University of Medical Science; Shoko I. Hagen, Oregon Health and Science University; Yasuko Tsunetsugu-Yokota, National Institute of Infectious Diseases; Francois Villinger, Emory University; Aftab Ansari, Emory University; Yasuo Suzuki, Japan Science and Technology Agency; Naoki Yamamoto, AIDS Research Center; Yoshiyuki Nagai, Center of Research Network for Infectious Diseases; Louis J. Picker, Oregon Health and Science University; Kazuyasu Mori, Japan Science and Technology Agency
• Language: English
• Date: 2012-09
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2012, American Society for Microbiology.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.00948-12
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 86
• Issue: 17
• Start Page: 9323
• End Page: 9336
• Grant/Funding Information: This study was supported by AIDS research grants from the Health Sciences Research Grants from the Ministry of Health, Labor, and Welfare in Japan and from the Ministry of Education, Culture, Sports, Science, and Technology in Japan.; This study was conducted through the Cooperative Research Program in the Tsukuba Primate Research Center, National Institute of Biomedical Innovation.
• Keywords: SIV INFECTION; MEMORY CELLS; Life Sciences & Biomedicine; RHESUS MACAQUES; PRODUCTIVE INFECTION; CD4(+) T-CELLS; Virology; GASTROINTESTINAL-TRACT; GP120 ENVELOPE GLYCOPROTEIN; CCR5 EXPRESSION; VIROLOGY; PRIMARY HIV-1 INFECTION; Science & Technology; SOOTY MANGABEYS
• Research Categories: Health Sciences, Immunology; Biology, Microbiology; Biology, Virology

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.