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

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 (5G) 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 tis-sues targeted by these viruses, where functionally and phenotypically different memory CD4 T cells reside. The results showed that5G replicates in secondary lymphoid tissue (SLT) at 1- to 2-log-lower levels than SIVmac239, whereas SIVmac239-infected but not5G-infected animals deplete CXCR3 CCR5 transitional memory (TrM) CD4 T cells. An early robust5G replica-tion 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