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Reverse transcriptase (RT)-independent as well as RT-dependent HIV-1 replication exists in syncytia following cell fusion.

We studied the role of reverse transcriptase (RT) in human immunodeficiency virus (HIV)-1 replication in syncytia following cell fusion. A chronically HIV-1-infected MOLT-4 (MOLT-4/IIIB) cells allow HIV-1 replication and induce syncytium formation between uninfected MOLT-4 cells. AZT (3'-azido-3'-deoxythymidine, 1 microM) inhibited neither HIV-1 replication in MOLT-4/IIIB cells nor the syncytium formation induced by concultivation of MOLT-4/IIIB cells with uninfected MOLT-4 cells. In the supernatant of the syncytium containing culture a remarkably higher titer of p24 antigen was produced than in that of MOLT/IIIB cell culture. AZT inhibited p24 antigen production by HIV-1 in the syncytia to levels to comparable to that in MOLT-4/IIIB cells which were treated with AZT. In addition, p24 production by HIV-1 in the syncytia formed by cocultivation of CL-2 cells, which are chronically infected with HIV-1 but lack functional RT, with uninfected MOLT-4 cells was not different from that in CL-2 cells alone. The results suggest that HIV-1 RT plays an important role in HIV-1 replication within the syncytia but an RT-independent replication process which is essential for syncytium formation also exists in the syncytia. These results indicate that not only RT inhibitors but also inhibitors of syncytium formation are essential for anti-HIV therapy.