Mj. Potash et al., HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION REQUIRES REVERSE TRANSCRIPTION OF NASCENT VIRAL-RNA, DNA and cell biology, 12(8), 1993, pp. 685-693
We have previously shown that during human immunodeficiency virus type
1 (HIV-1) infection in vitro continued reverse transcription is requi
red for stable HIV-1 production, but entry by progeny virus is not. To
determine the source of the viral RNA reverse-transcribed late in inf
ection, we employed inhibitors of HIV-1 transmission, reverse transcri
ption, and proteolysis of the Gag-Pol polyprotein to interrupt HIV-1 i
nfection in vitro. The kinetics of synthesis of viral DNA, RNA, and pr
oteins was examined. During single-cycle infection, inhibition of reve
rse transcription 24-72 hr after infection delayed production of viral
RNA and protein 10 days. Although viral DNA was detected in Southern
blots, inhibition of Gag-Pol processing or transient inhibition of rev
erse transcription blocked its expression. We propose that after initi
al reverse transcription of input virion RNA is complete, newly synthe
sized HIV-1 RNA is reverse-transcribed before its export in virions to
yield the viral DNA required for stable HIV-1 production.