J. Virol., Sep 1996, 5840-5844, Vol 70, No. 9
Copyright © 1996, American Society for Microbiology

Conditional human immunodeficiency virus type 1 protease mutants show no role for the viral protease early in virus replication

AH Kaplan, M Manchester, T Smith, YL Yang and R Swanstrom
Department of Medicine, University of California at Los Angeles 90024, USA.

The human immunodeficiency virus type 1 protease plays a critical role in the proteolytic processing of precursor polyproteins during virion maturation. Contradictory evidence has been obtained for a possible role for the protease early after infection, i.e., during DNA synthesis and/or integration. We have reexamined this question by using conditional mutants of the protease. In one set of experiments, protease mutants that confer a temperature-sensitive phenotype for processing were used to assess the need for protease activity early after infection. No significant difference from results with wild-type virus was seen when infections were carried out at either 35 or 40 degrees C. In a separate set of experiments, infections were carried out in the presence of a protease inhibitor. In this case, both wild- type virus and a drug-resistant variant were used, the latter as a control to ensure a specific effect of the inhibitor. Infection with either virus was not inhibited at drug concentrations that were up to 10-fold higher than those needed to inhibit intracellular processing by the viral protease. The results obtained by both of these experimental protocols provide evidence that the human immunodeficiency virus type 1 protease does not play a role early after infection.

This article has been cited by other articles:

• Tozser, J., Shulenin, S., Young, M. R., Briggs, C. J., Oroszlan, S. (2006). Replication-dependent fitness recovery of Human immunodeficiency virus 1 harbouring mutations of Asn17 of the nucleocapsid protein.. J. Gen. Virol. 87: 961-965 [Abstract] [Full Text]  
• Gruber, A., Wheat, J. C., Kuhen, K. L., Looney, D. J., Wong-Staal, F. (2001). Differential Effects of HIV-1 Protease Inhibitors on Dendritic Cell Immunophenotype and Function. J. Biol. Chem. 276: 47840-47843 [Abstract] [Full Text]  
• Nascimbeni, M., Lamotte, C., Peytavin, G., Farinotti, R., Clavel, F. (1999). Kinetics of Antiviral Activity and Intracellular Pharmacokinetics of Human Immunodeficiency Virus Type 1 Protease Inhibitors in Tissue Culture. Antimicrob. Agents Chemother. 43: 2629-2634 [Abstract] [Full Text]