The downregulation of CD4 has been widely reported during HIV infection, and this downregulation is thought to be caused by Nef proteins for stimulating HIV-1 production and infectivity.55–57Upregulation of CCR5 may be important in susceptibility to infection because it serves as a critical receptor for HIV and SIV infection, and its modulation correlated with infectability.58,59. Here, CD4 is linked to HIV infectious disease.