HUMAN-COMPLEMENT COMPONENT C1Q INHIBITS THE INFECTIVITY OF CELL-FREE HTLV-I

Human T cell leukemia virus type I (HTLV-I) is a retrovirus that is no t lysed by human serum or complement. It has not been determined, howe ver, whether HTLV-I directly binds to complement components or whether it retains infectivity after incubation with human serum. We investig ated the effects of human serum on the infectivity of cell-free HTLV-I produced by human and animal cells. Plating of vesicular stomatitis v irus (HTLV-I) pseudotypes prepared in cat or human cells and formation of HTLV-I DNA after infection of cell-free HTLV-I produced by cat or human cells were markedly inhibited by treatment with fresh human seru m, but not by heat-inactivated serum. HTLV-I infection was also inhibi ted by treatment with C2-, C3-, C6-, or C9-deficient serum, but not by Clq-deficient serum. Inhibitory activities of normal human serum agai nst HTLV-I were neutralized by anti-Clq serum. Furthermore, purified C lq inhibited HTLV-I infection. The direct binding of Clq to HTLV-I was confirmed by comigration of Clq with HTLV-I virion upon sucrose densi ty gradient ultracentrifugation of HTLV-I virion treated with Clq. Bin ding assay using synthetic envelope peptides indicated that Clq bound to an extramembrane region of the gp21 transmembrane protein. These fi ndings indicate that the human complement component Clq inactivates HT LV-I infectivity.