One possible explanation is that a small fraction of CD4 and CXCR4 on PBMCs, but not on MT4 cells, are sufficient for HIV-1 infection; as a result, partial down regulation of CD4 and CXCR4 potently inhibits HIV-1 infection of MT4 cells but is not effective against ×4 virus infection of PBMCs. Here, CD4 is linked to viral infectious disease.