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

J Virol. 2012 Sep;86(17):9323-36. doi: 10.1128/JVI.00948-12. Epub 2012 Jun 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Products, env / genetics
  • Gene Products, env / metabolism*
  • Glycosylation
  • HIV / genetics
  • HIV / immunology
  • HIV / metabolism
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • Immune System / immunology*
  • Immune System / virology
  • Immunologic Memory
  • Intestines / immunology
  • Intestines / virology
  • Macaca mulatta
  • Organ Specificity
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology*
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / metabolism*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / virology

Substances

  • Gene Products, env