CD4-independent infection of two CD4(-)/CCR5(-)/CXCR4(+) pre-T-cell lines by human and simian immunodeficiency viruses

The infection of CD4-negative cells by variants of tissue culture-adapted h uman immunodeficiency virus type 1 (HIV-1) or HIV-2 strains has been shown to be mediated by the CXCR4 coreceptor. Here we show that two in vitro-esta blished CD4(-)/CCR5(-)/CXCR4(+) human pre-T-cell lines (A3 and A5) can be p roductively infected by wild-type laboratory-adapted T-cell-tropic HIV-1 an d HIV-2 strains in a CD4-independent, CXCR4-dependent fashion. Despite the absence of CCR5 expression, A3 and A5 cells were susceptible to infection b y the simian immunodeficiency viruses SIVmac239 and SIVmac316. Thus, at lea st in A3 and A5 cells, one or more of the chemokine receptors can efficient ly support the entry of HIV and SIV isolates in the absence of CD4. These f indings suggest that to infect cells of different compartments, HIV and SIV could have evolved in vivo to bypass CD4 and to interact directly with an alternative receptor.