DENOVO REVERSE TRANSCRIPTION IS A CRUCIAL EVENT IN CELL-TO-CELL TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS

The proposal that replication of human immunodeficiency virus type 1 (HIV-1), mediated by cell-to-cell transmission of the virus, might bypass de novo reverse transcription was tested by using one-step cell-to-cell and cell-free virus infection systems. Two well characterized reverse transcriptase (RT) inhibitors, azidothymidine at 20-mu-M and phosphonoformic acid at 100-mu-g/ml, blocked HIV replication completely following both cell-free virus and cell-to-cell transmission infection, as determined from the kinetics of unintegrated viral DNA synthesis and supernatant RT production after virus infection. Our results confirm that de novo reverse transcription is a crucial and mandatory event in HIV-1 replication following cell-to-cell transmission of the virus.