Polymorphic LEDGF/p75 variants support efficient HIV-1 infection ex vivo

摘要

HIV-1 replication relies on the interactions with numerous cellular factors, and genetic polymorphisms in the human population can significantly effect progression to AIDS. Lens epithelium-derived growth factor (LEDGF)/p75 is a crucial cellular cofactor that directs HIV-1 integration to active genes. The N-terminal elements, which include a Pro-Trp-Trp-Pro (PWWP) domain, confer constitutive binding to chromatin, whereas the downstream integrase (IN)-binding domain (IBD; residues 347-429) binds lentiviral IN protein. IBD or PWWP domain point mutations can render LEDGF/p75 nonfunctional in ex-vivo models of HIV-1 infection.