Identification of HIV-1 Envelope Mutations that Enhance Entry Using Macaque CD4 and CCR5.

ABSTRACT: Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque CD4 that results in reduced HIV-1 Envelope (Env)-mediated viral entry compared to human CD4. Recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in Env's gp120 subunit that enhance binding of macaque CD4 by transmitted/founder HIV-1 viruses. In order to identify additional Env mutations that promote infection of macaque cells, we utilized deep mutational scanning to screen thousands of Env point mutants for those that enhance HIV-1 entry via macaque

SUBMITTER: Roop JI 

PROVIDER: S-EPMC7077290 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature