FIG 8.

Fitness costs of escape variants vary across sites in the C-terminal heptad repeat of gp41. (A) Frequency of variants at sites 640, 641, and 644 within Env_635-649 over 247 dps of follow-up. (B) Magnitude of IFN-γ response to 15-mers reflecting variation in Env_635-649 at 53 dps (open bars) and 247 dps (filled bars). All variants are color coordinated between graphs A and B. Optimal epitopes are boxed. (C) NL9 epitope (founder EC₅₀ of 51 ng/ml, black; A₆₃₈ EC₅₀ of 4,786 ng/ml, gray squares; R₆₄₅ EC₅₀ of 15,849 ng/ml, gray triangles) in PIC38417 at 53dps. (D) The gp41 C-terminal and N-terminal heptad repeats bind to facilitate viral fusion. Interacting amino acids are circled and linked. The NL9 epitope is circled in purple (58). (E) Fitness costs of observed and hypothetical NL9 epitope variants relative to S640/L641/T644 within an otherwise homologous HIV-1_NL4-3 background.