Role of HIV Envelope Proteins In Viral Replication and HIV Pathogenesis

National Institute Of Allergy And Infectious Diseases

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Abstract

In the past year we demonstrated that MAdCAM and retinoic acid (RA), two constituents of gut tissues, together with TGF-beta, promote the differentiation of CD4+ T cells into alpha4beta7+CD69+CD103+ cells consistent with TRMs. These cells also express CCR5 and CCR9. CCR5 renders these cells susceptible to HIV infection, despite the anti-proliferative action of TGF-beta. Formation of TRMs was reduced by MAdCAM antagonists developed to treat inflammatory bowel diseases. Of note, CD4+ tissue resident memory T cells (TRMs) are implicated in the formation of persistent HIV reservoirs that are established in the very early stages of infection. The tissue-specific factors that direct T cells to establish tissue residency are not well defined, as is the case for the factors that establish viral latency. Our findings help explain the contribution of CD4+ TRMs to persistent viral reservoirs and HIV pathogenesis.