Conditional human immunodeficiency virus type 1 protease mutants show no role for the viral protease early in virus replication.
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.
Kaplan
A H
AH
Department of Medicine, University of California at Los Angeles 90024, USA.
Manchester
M
M
Smith
T
T
Yang
Y L
YL
Swanstrom
R
R
D002460:Cell Line; D015683:Gene Products, gag / Q000096:biosynthesis*; D016333:HIV Protease / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D013696:Temperature; D014779:Virus Replication
D015683:Gene Products, gag; D011498:Protein Precursors; D011994:Recombinant Proteins; D016333:HIV Protease