Large scale all-atom molecular dynamics simulations of mutant CA tubes provide insights on cytotoxic T-lymphocyte-mediated HIV-1 restriction

For certain HIV-1-infected individuals, viral replication is controlled via expression of human leukocyte antigens (HLA). HLAs mark infected cells for host-mediated elimination by exposing viral epitopes to CD8+ cytotoxic T-lymphocytes (CTL). For HLA-B27, CTLs target and attack the HIV-1 capsid protein (CA), particularly the CA-derived KK10 epitope. Substitution mutation of Arginine at position 264 to Lysine (R264K) enables HIV-1 to escape the host CTL response but limits infectivity. Through a multi-pronged approach, employing both experimental and computational methods, we show that impairment of R264K mutant infectivity results from stymied viral DNA integration.