Contribution of multiple rounds of viral entry and reverse transcription to expression of human immunodeficiency virus type 1. A quantitative kinetic study

Abstract

Human immunodeficiency virus 1 (HIV-1) infection in vitro has been analyzed by the kinetics of expression of HIV-1 RNA and antigens during treatment with antiviral agents. Intracellular HIV-1 RNA rose from input values of 15 molecules per cell to 28 molecules per cell within 3 h after infection and reached a peak of 13,125 in 5 days. The first detectable increase in levels of HIV-1 capsid protein production was 1 day after infection. Virus infection was interrupted at different time points by the introduction of either 2',3'-dideoxycytidine, 3'-azido-3'-deoxythymidine, or suramin to block reverse transcription, or recombinant soluble CD4 to block binding and re-entry of progeny virus. Two results are noteworthy. First, the three inhibitors of reverse transcription blocked viral expression when added up to 48 h after infection. Second, the extent of infection, although postponed, is not greatly altered by culture of infected cells in recombinant soluble CD4. These data imply that reinfection with progeny virus, while necessary for rapid virus expression, is not required for the establishment of productive HIV-1 infection.