URL: https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.

Both activated and resting CD4 ؉ T cells in mucosal tissues play important roles in the earliest phases of infection after sexual transmission of HIV-1, a process that is inefficient. HIV-1 gp120 binds to integrin ␣4␤7 (␣4␤7), the gut mucosal homing receptor. We find that ␣4␤7 high CD4 ؉ T cells are more susceptible to productive infection than are ␣4␤7 low-neg CD4 ؉ T cells in part because this cellular subset is enriched with metabolically active CD4 ؉ T cells. ␣4␤7 high CD4 ؉ T cells are CCR5 high and CXCR4 low ; on these cells, ␣4␤7 appears in a complex with CD4. The specific affinity of gp120 for ␣4␤7 provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission.integrin receptor ͉ transmission ͉ gut-associated lymphoid tissues (GALT)

No abstract

Human immunodeficiency virus (HIV) infection leads to numerous perturbations of B cells through mechanisms that remain elusive. We performed DNA microarray, phenotypic, and functional analyses in an effort to elucidate mechanisms of B cell perturbation associated with ongoing HIV replication. 42 genes were up-regulated in B cells of HIV-viremic patients when compared with HIV-aviremic and HIV-negative patients, the majority of which were interferon (IFN)-stimulated or associated with terminal differentiation. Flow cytometry confirmed these increases and indicated that CD21low B cells, enhanced in HIV-viremic patients, were largely responsible for the changes. Increased expression of the tumor necrosis factor (TNF) superfamily (TNFSF) receptor CD95 correlated with increased susceptibility to CD95-mediated apoptosis of CD21low B cells, which, in turn, correlated with HIV plasma viremia. Increased expression of BCMA, a weak TNFSF receptor for B lymphocyte stimulator (BLyS), on CD21low B cells was associated with a concomitant reduction in the expression of the more potent BLyS receptor, BAFF-R, that resulted in reduced BLyS binding and BLyS-mediated survival. These findings demonstrate that altered expression of genes associated with IFN stimulation and terminal differentiation in B cells of HIV-viremic patients lead to an increased propensity to cell death, which may have substantial deleterious effects on B cell responsiveness to antigenic stimulation.