3rd International Workshop on HIV Drug Resistance 2-5 August 1994, Kauai, Hawaii, USA

THE BIOLOGICAL ROLE AND THERAPEUTIC SIGNIFICANCE OF DNA IN HIV-1 VIRIONS

Int Wkshop HIV Drug Res 1994 Aug 2-5;3:37 (abstract no. 36)

P. Krogstad¹, J.A. Zack², and I.S.Y. Chen^3
1Department of Pediatrics, ²Department of Medicine, ³Department of Microbiology & Immunology, UCLA School of Medicine, Los Angeles, CA, USA

We previously demonstrated that partially reverse transcribed DNA is synthesized in quiescent peripheral blood lymphocytes (PBU after infection by human immunodeficiency virus type 1 (HIV-1). However, others have recently reported detection of partially reverse transcribed DNA associated with purified HIV-1 virions, and suggested that this virion-associated DNA may play a role in productive infection. If so, the efficacy of reverse transcriptase inhibitors as therapeutic agents for HIV-1 infection could be compromised. We therefore quantitatively analyzed the structure and biological role of virion-associated HIV-1 DNA and compared it to the biological activity of DNA genomes synthesized after penetration of target cell PBL’s. We confirmed that only partially reverse transcribed DNA is detected after infection of quiescent lymphocytes when effective measures are taken to remove DNA contamination from viral stocks. Using quantitative polymerase chain reaction (PCR) analysis, we find that virion-associated DNA is composed of partial reverse transcripts and that these virion-associated DNA molecules give rise to a small proportion (<5%) of HIV-1 DNA found in cells 24 hours post-infection. Limiting dilution analysis revealed no difference in the infectivity of virus stocks produced in the presence or absence of azidothymidine. We conclude that reverse transcriptase inhibitors interfere with virus replication by inhibiting de novo synthesis of viral DNA occuring after virions enter PBL, and that virion-associated DNA appears to play, at most, a minor role in the HIV-1 lifecycle.

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1994-08-02
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