REVERSE TRANSCRIPTION TAKES PLACE WITHIN EXTRACELLULAR HIV-1 VIRIONS - POTENTIAL BIOLOGICAL SIGNIFICANCE

Extracellular HIV-1 virions purified from cell culture supernatants ha ve been found to contain viral DNA that is the result of partial rever se transcription within the virus particles. Our data supported these observations and further indicated that the ratio of genomic RNA to vi ral DNA was approximately 10(3):1 for the ''strong stop'' (R-U5) regio n and 10(5):1 for the gag region. We have shown that, in the absence o f detergent, large amounts of DNase-resistant viral DNA can be synthes ized within intact HIV-1 virions, indicating that this phenomenon is n ot dependent on perturbation of the viral envelope. Nascent viral DNA synthesis also occurred in purified virions incubated at 37-degrees-C in cell-free human physiological fluids including seminal plasma, bloo d plasma, breast milk, and fecal fluid. In vitro HIV-1 infection assay s, in which HIV-1 DNA synthesis was initiated in HIV-1 virions by prio r incubation with deoxyribonucleoside triphosphates, demonstrated that virus particles so treated had an increased infectious titer over unt reated virions when incubated with target human T cells. Our data sugg est that HIV-1 virion-associated DNA synthesis may occur in vivo and m ay impact on the efficiency of intra- and interhost virus transmission . If so, this phenomenon should prove to be an important target for an tiviral therapeutic strategies.