Glycosylation of simian immunodeficiency virus influences immune-tissue targeting during primary infection, leading to immunodeficiency or viral control.
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.
AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
Chie
C
Sugimoto
Shinichiro
S
Nakamura
Shoko I
SI
Hagen
Yasuko
Y
Tsunetsugu-Yokota
Francois
F
Villinger
Aftab A
AA
Ansari
Yasuo
Y
Suzuki
Naoki
N
Yamamoto
Yoshiyuki
Y
Nagai
Louis J
LJ
Picker
Kazuyasu
K
Mori
D000818:Animals; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006678:HIV / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000821:virology; D007156:Immunologic Memory; D007422:Intestines / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D009928:Organ Specificity; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology
D015686:Gene Products, env