Acquired immune deficiency syndrome (AIDS) was first defined in the early 1980s as a new infectious disease caused by HIV, which leads to a progressive depletion of CD4+ T cells as its hallmark (1, 2). Within a short time, it quickly became clear that CD4, a TCR coreceptor, was also the major receptor for entry of HIV into CD4+ T cells (3). However, it was puzzling that expression of a CD4 transgene rendered human cells, but not mouse cells, permissive for HIV infection. This key finding suggested the presence of one or more human cofactor(s) required for HIV cell entry. Furthermore, it was shown that two HIV isolates had different tropisms for the infection of target cells in vitro. HIV strains that were able to infect primary macrophages and T cells, but not CD4+ human immortalized T cell lines, were present during...

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