Integrin alpha4beta7 is downregulated on the surfaces of simian immunodeficiency virus SIVmac239-infected cells

Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infection results in an early and enduring depletion of intestinal CD4(+) T cells. SIV and HIV bind integrin alpha4beta7, thereby facilitating infection of lymphocytes that home to the gut-associated lymphoid tissue (GALT). Using an ex vivo flow cytometry assay, we found that SIVmac239-infected cells expressed significantly lower levels of integrin alpha4beta7 than did uninfected cells. This finding suggested a potential viral effect on integrin alpha4beta7 expression. Using an in vitro model, we confirmed that integrin alpha4beta7 was downregulated on the surfaces of SIVmac239-infected cells. Further, modulation of integrin alpha4beta7 was dependent on de novo synthesis of viral proteins, but neither cell death, the release of a soluble factor, nor a change in activation state was involved. Downregulation of integrin alpha4beta7 may have an unappreciated role in the CD4 depletion of the mucosal-associated lymphoid compartments, susceptibility to superinfection, and/or immune evasion.