Isolation of primary HIV-1 that target CD8+ T Lymphocytes using CD8 as a receptor

HIV-1 use CD4 receptors to infect their primary targets, CD4(+) cells, whereas CD8(+) cells have a protective role against HIV-1. We recently isolated HIV-1-producing CD8(+) clones from two AIDS patients. Here we show that although HIV-1 produced by CD8(+) cells maintained the ability to infect CD4(+) cells, these viruses were able to infect CD8(+) cells independent of CD4. Evidence indicates that these viruses used CD8 as a receptor to infect CD8(+) cells. First, expression of CD8 was downmodulated after infection. Second, anti-CD8 antibodies blocked viral entry and replication in CD8(+) cells. Finally, resistant cells became susceptible after expression of CD8. Although these viruses used CXCR4 to enter CD4(+) cells, it seems that infection of CD8(+) cells was independent of CXCR4 or CCR5 co-receptors. Novel changes were observed in envelope sequences of CD8-tropic viruses. These results provide initial evidence that HIV-1 can mutate to infect CD8(+) cells using CD8 as a receptor.