Effects of Reduced Gag Cleavage Efficiency on HIV-1 Gag-Pol Package

Overview

Journal BMC Microbiol

Publisher Biomed Central

Specialty Microbiology

Date 2022 Apr 9

PMID 35395730

Authors

Yi-Ru Lin

Shih-Ming Chu

Fu-Hsien Yu

Kuo-Jung Huang

Chin-Tien Wang

Affiliations

Soon will be listed here.

Abstract

Background: HIV-1 pol, which encodes enzymes required for virus replication, is initially translated as a Gag-Pol fusion protein. Gag-Pol is incorporated into virions via interactions with Gag precursor Pr55. Protease (PR) embedded in Gag-Pol mediates the proteolytic processing of both Pr55gag and Gag-Pol during or soon after virus particle release from cells. Since efficient Gag-Pol viral incorporation depends on interaction with Pr55 via its N-terminal Gag domain, the prevention of premature Gag cleavage may alleviate Gag-Pol packaging deficiencies associated with cleavage enhancement from PR.

Results: We engineered PR cleavage-blocking Gag mutations with the potential to significantly reduce Gag processing efficiency. Such mutations may mitigate the negative effects of enhanced PR activation on virus assembly and Gag-Pol packaging due to an RT dimerization enhancer or leucine zipper dimerization motif. When co-expressed with Pr55, we noted that enhanced PR activation resulted in reduced Gag-Pol cis or trans incorporation into Pr55 particles, regardless of whether or not Gag cleavage sites within Gag-Pol were blocked.

Conclusions: Our data suggest that the amount of HIV-1 Gag-Pol or Pol viral incorporation is largely dependent on virus particle production, and that cleavage blocking in the Gag-Pol N-terminal Gag domain does not exert significant impacts on Pol packaging.

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