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. 1996 Jun;70(6):3392–3400. doi: 10.1128/jvi.70.6.3392-3400.1996

Targeting human immunodeficiency virus type 1 reverse transcriptase by intracellular expression of single-chain variable fragments to inhibit early stages of the viral life cycle.

F Shaheen 1, L Duan 1, M Zhu 1, O Bagasra 1, R J Pomerantz 1
PMCID: PMC190211  PMID: 8648670

Abstract

Novel molecular approaches to inhibit human immunodeficiency virus type 1 (HIV-1) infection have received increasing attention because of the lack of effective antiviral drug therapies in vivo. We now demonstrate that cells can be intracellularly immunized by cytoplasmic expression of single-chain variable antibody fragments (SFv) which bind to the HIV-1 reverse transcriptase (RT) enzyme. The expression of anti-RT SFv in T-lymphocytic cells specifically neutralizes the RT activity in the preintegration stage and affects the reverse transcription process, an early event of the HIV-1 life cycle. Blocking the virus at these early stages dramatically decreased HIV-1 propagation, as well as the HIV-1-induced cytopathic effects in susceptible human T lymphocytes, by impeding the formation of the proviral DNA. These data also demonstrate that intracellular, complete SFvs may gain access to viral proteins of the HIV-1 preintegration complex. These SFvs will provide a tool with which to better understand the molecular mechanisms involved in restricting viral replication in HIV-1-infected cells.

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Selected References

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