DECAY-ACCELERATING FACTOR (CD55) PROTECTS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FROM INACTIVATION BY HUMAN-COMPLEMENT

HIV-1, in contrast to animal retroviruses; is not lysed by human compl ement, but is readily inactivated by the sera from different animal sp ecies. To identify a possible species-specific protection mechanism, H IV-1 was expressed in cells of non-human origin. Recombinant HIV-1 vir ions that could encode the chloramphenicol acetyltransferase (CAT) pro tein were produced in African green monkey COS-1 cells, mink cells and , as a control, in human HEp-2 cells and were then used to infect CD4- positive target cells. Analysis of the CAT activity of the target cell s revealed that fresh HIV-l-negative human serum reduced the infectivi ty of HIV-1 derived from monkey and mink cells five- to tenfold, but h ad no effect on HIV-1 produced in human cells. In addition, human seru m efficiently lysed HIV-1 produced in non-human cells in contrast to H IV-1 originating from human cells, suggesting lysis as an important me chanism of virus inactivation. Mammalian cells are protected against l ysis by homologous complement by membrane-bound regulatory molecules. Two of these complement inhibitors, namely decay-accelerating factor ( DAF) and, to a lesser extent, CD59 were found on the surface of HIV-1 virions by means of a virus capture assay. Antibodies against DAF, but not against other host cell molecules found on the viral surface, eff iciently blocked the resistance of HIV-1 produced in human cells to hu man complement. These results suggest that the acquisition of DAF duri ng the budding process from human cells protects HIV-1 in a species-sp ecific way against the attack of human complement.