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Replacement of the P1 Amino Acid of Human Immunodeficiency Virus Type 1 Gag Processing Sites Can Inhibit or Enhance the Rate of Cleavage by the Viral Protease
Journal article   Open access   Peer reviewed

Replacement of the P1 Amino Acid of Human Immunodeficiency Virus Type 1 Gag Processing Sites Can Inhibit or Enhance the Rate of Cleavage by the Viral Protease

Steve C. Pettit, Gavin J. Henderson, Celia A. Schiffer and Ronald Swanstrom
Journal of virology, v 76(20), pp 10226-10233
01 Oct 2002
DOI: https://doi.org/10.1128/JVI.76.20.10226-10233.2002
PMID: 12239298
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1128/jvi.76.20.10226-10233.2002View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

ABSTRACT Processing of the human immunodeficiency virus type 1 (HIV-1) Gag precursor is highly regulated, with differential rates of cleavage at the five major processing sites to give characteristic processing intermediates. We examined the role of the P1 amino acid in determining the rate of cleavage at each of these five sites by using libraries of mutants generated by site-directed mutagenesis. Between 12 and 17 substitution mutants were tested at each P1 position in Gag, using recombinant HIV-1 protease (PR) in an in vitro processing reaction of radiolabeled Gag substrate. There were three sites in Gag (MA/CA, CA/p2, NC/p1) where one or more substitutions mediated enhanced rates of cleavage, with an enhancement greater than 60-fold in the case of NC/p1. For the other two sites (p2/NC, p1/p6), the wild-type amino acid conferred optimal cleavage. The order of the relative rates of cleavage with the P1 amino acids Tyr, Met, and Leu suggests that processing sites can be placed into two groups and that the two groups are defined by the size of the P1′ amino acid. These results point to a trans effect between the P1 and P1′ amino acids that is likely to be a major determinant of the rate of cleavage at the individual sites and therefore also a determinant of the ordered cleavage of the Gag precursor.

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Collaboration types
Domestic collaboration
Web of Science research areas
Virology
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