The role of tetraspanin pretein CD63 in humna immunodeficiency virus type 1 infection and replication




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Human Immunodeficiency Virus (HIV) infection typically involves interaction of Env with CD4 and a chemokine coreceptor, either chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor (CXCR4). Other cellular factors supporting HIV replication have recently been characterized. Previous works demonstrated a role for CD63 in early HIV infection events in macrophages via inhibition by pretreatment of an anti-CD63 antibody, which did not inhibit HIV replication in peripheral blood lymphocytes or in two CD4+ cell lines tested. To confirm the requirement for CD63 in HIV replication, CD63 expression in cells was decreased by RNA interference using short interfering RNAs (siRNA). Inhibition of HIV replication was demonstrated in macrophages following CD63-specific siRNA treatment. The inhibition effect was also shown when the anti-CD63 antibody treatment was delayed 12 hours after HIV infection, or by CD63 siRNA treatment 72 hours post infection, suggesting that late HIV replication events may also be affected. In U373-MAGI cells engineered to stably express either CCR5 or CXCR4, CD63-specific siRNA treatment resulted in over 90% reduction in CD63, which was associated with decreased HIV replication, even though these cells were refractory to HIV inhibition by the anti-CD63 antibody treatment. Using an R5/X4 HIV-89.6, CD63 downregulation was shown to decrease HIV replication in the U373-MAGI cells expressing either CCR5 or CXCR4. Although anti-CD63 antibody was previously shown to inhibit early HIV infection events only in macrophages, current progress shows a role for CD63 in HIV replication in CD4+ cell lines. Further delineation of the role of CD63 in HIV replication may lead to development of novel therapeutic compounds.