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.
Budde
Melisa L
ML
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Lhost
Jennifer J
JJ
Dudley
Dawn M
DM
Rakasz
Eva G
EG
O'Connor
David H
DH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000821:virology*; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*
D016023:Integrins; C071777:integrin alpha4beta7
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