Affiliation:
1. Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD
Abstract
Abstract
HIV infects and replicates in CD4+ T cells but effects on host immunity and disease also involve depletion, hyper-activation, and modification of CD4-negative cell populations. In particular, the depletion of CD4-negative γδ T cells is common to all HIV+ individuals. We found that soluble or cell-associated envelope glycoproteins from CCR5-tropic strains of HIV could bind, activates the p38-caspase pathway, and induce the death of γδ cells. Envelope binding requires integrin α4β7 and chemokine receptor CCR5 which are at high levels and form a complex on the γδ T cell membrane. This receptor complex facilitated V3 loop binding to CCR5 in the absence of CD4-induced conformational changes. Cell death was increased by antigen stimulation after exposure to envelope glycoprotein. Direct signaling by envelope glycoprotein killed CD4-negative γδ T cells and reproduced a defect observed in all patients with HIV disease.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference56 articles.
1. Pathogenic mechanisms of HIV disease.;Moir;Annu Rev Pathol,2011
2. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells.;Li;Nature,2005
3. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection.;Mattapallil;Nature,2005
4. B cells in HIV infection and disease.;Moir;Nat Rev Immunol,2009
5. Inhibition of natural killer cell activities from normal donors and AIDS patients by envelope peptides from human immunodeficiency virus type I.;Nair;Cell Mol Biol (Noisy-le-grand),1997
Cited by
44 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献