HIV Nef-mediated WAVE2-ARP2/3 inhibition underlies CD4 ⁺ T-cell lamellipodial abnormalities and immune dysfunction

CD4⁺ T cells migrate throughout the body and form immune synapses to carry out their functions. Both of these actions require dynamic actin structures, which are disrupted by HIV proteins. Our study suggests that a key HIV protein, Nef, might disrupt a vital internal cellular machinery that helps immune cells move and function properly. Our microscopic and proteomics studies suggest a new model in which Nef inhibits a large protein complex at the front of migrating T cells. Restoring this cytoskeletal dysfunction may be key to restoring CD4⁺ T-cell survival and function, which may improve adaptive immune responses during HIV infection.