Modulation of CD4, CXCR-4, and CCR-5 makes human hematopoietic progenitor cell lines infected with human herpesvirus-6 susceptible to human immunodeficiency virus type 1

Two CD34(+) human hematopoietic progenitor cell (HPC) lines, KG-1 and TF-1, became susceptible to human immunodeficiency virus type 1 (HIV-1) infectio n in the presence of a concurrent infection by human herpesvirus-6 (HHV-6). We have analyzed the possible mechanism(s) underlying this phenomenon in l ight of the recent demonstration that at least two members of the chemokine receptor family, CXCR4 (LESTR/fusin) and CCR5 molecules, are the HIV-1-spe cific coreceptors necessary, together with the high-affinity receptor CD4, for entry into target cells of T-tropic and M-tropic HIV-1 isolates, respec tively. KG-1 cells show CXCR4 and CCR5 surface molecules in a large proport ion of the cell population. Therefore, their susceptibility to both T-tropi c and M-tropic HIV-1 strains, caused by HHV-6 infection, can be explained b y the HHV-6-induced appearance of CD4 molecules in about 40% of the cell po pulation. In TF-1 cells, 10%-15% of which are CD4(+) and exhibit a consiste nt CCR5 presence in a large proportion of the cell population and a hardly detectable amount of CXCR4 in a very limited number of cells, HHV-6 infecti on does not modify the cell surface availability of HIV-1-specific high-aff inity receptor or coreceptors.