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. 1996 Sep;70(9):5840–5844. doi: 10.1128/jvi.70.9.5840-5844.1996

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

A H Kaplan 1, M Manchester 1, T Smith 1, Y L Yang 1, R Swanstrom 1
PMCID: PMC190600  PMID: 8709202

Abstract

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.

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Selected References

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