FACTORS SECRETED BY HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I)-INFECTED CELLS CAN ENHANCE OR INHIBIT REPLICATION OF HIV-1 IN HTLV-I-UNINFECTED CELLS - IMPLICATIONS FOR IN-VIVO COINFECTION WITH HTLV-I AND HIV-1

It remains controversial whether human T lymphotropic virus type I (HT LV-I) coinfection leads to more rapid progression of human immunodefic iency virus (HIV) disease in dually infected individuals. To investiga te whether HTLV-I infection of certain cells can modulate HIV-1 infect ion of surrounding cells, primary CD4(+) T cells were treated with cel l-free supernatants from HTLV-I-infected MT-2 cell cultures. The prima ry CD4(+) T cells became resistant to macrophage (M)-tropic HIV-1 but highly susceptible to T cell (T)-tropic HIV-1. The CC chemokines RANTE S (regulated on activation, normal T cell expressed and secreted), mac rophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta in the MT-2 cell supernatants were identified as the major suppressive factors fo r M-tropic HIV-1 as well as the enhancers of T-tropic HIV-1 infection, whereas soluble Tax protein increased susceptibility to both M-and T- tropic HIV-1. The effect of Tax or CC chemokines on T-tropic HIV-1 was mediated, at least in part, by increasing HIV Env-mediated fusogenici ty. Our data suggest that the net effect of HTLV-I coinfection in HIV- infected individuals favors the transition from M-to T-tropic HIV phen otype, which is generally indicative of progressive HIV disease.