A CD63 mutant inhibits T-cell tropic human immunodeficiency virus type 1 entry by disrupting CXCR4 trafficking to the plasma membrane.

We have discovered that an N-terminal deletion mutant of a membrane protein, CD63, (CD63DeltaN) blocks entry of CXCR4-using, T-cell tropic human immunodeficiency virus type 1 (X4 HIV-1) by suppressing CXCR4 surface expression. This suppression was observed for CXCR4 but not for CD4, CCR5, CD25, CD71 or other tetraspanin proteins. The suppression of CXCR4 expression on the plasma membrane appeared to be caused by mislocalization of CXCR4 and exclusive transportation of CXCR4 toward intracellular organelles, mainly late endosomes/lysosomes. Our data suggest that CXCR4 trafficking can be modified in terms of its recruitment to the plasma membrane without enhancing the degradation or arresting vesicular transport of CXCR4.