Jean-Charles Grivel, Yoshinori Ito, Wendy Fitzgerald, Silvia Chen, Yana Kiselyeva and Leonid Margolis. National Institutes of Health, Bethesda, MD (USA).

In HIV-1 infected individual virus quickly diverges into a “swarm” of quasi-species.  The dominance of viral variants may change in the course of infection For example CCR5-utilizing (R5) HIV-1 variants generally dominate early stages of disease, whereas later CXC4-using variants (R5/X4 or X4) evolve.  Evolution of viral quasi-species may modulate the disease progression. Mechanisms of these phenomena are not fully understood. We addressed these problems in human lymphoid tissue infected ex vivo with R5, R5/X4 and X4 HIV-1 variants. X4 variants induce apoptosis in the majority of CD4+T cells that express CXCR4 resulting in a severe depletion of CD4+T cells, whereas R5 variants affect the minority of CD4+ T cells that express CCR5.  In model viral swarms of R5/X4 variants X4 infection inhibits R5 replication, and such inhibition is associated with an upregulation of CC-chemokines. The effects of infections by co-pathogens, such as human herpes virus 6 on HIV replication are discussed. Inhibition of R5 infection by CXCR4-utilizing HIV-1 may be contribute to X4 dominance thus accelerating disease progression. In general, interactions between HIV-1 quasi-species and between HIV-1 and its copathogens may be critical factors can be potentially used to modulate HIV disease.