Antibody Recognition of CD4-Induced Open HIV-1 Env Trimers—Yang 2022

After binding to CD4 and a coreceptor, HIV-1 envelope (Env), a heterotrimer comprising gp120-gp41 subunits, fuses viral and host cell membranes. CD4 binding rearranges Env trimer, resulting in CD4i open Env. One class of antibodies recognizes the CD4i open Env shape, according to structural investigations of antibodies from infected donors. We characterized HIV-1-infected donors' V2i MAbs, which resembled CD4i antibodies. V2i MAbs prefer CD4-bound open Env trimers in binding studies. V2i MAbs recognized the gp120 V1V2 domain and the β2/β3 strands on a CD4i open conformation Env using different angles of approach, but they did not directly interact with CD4. CG10, a CD4i antibody from mice inoculated with a gp120-CD4 complex, coupled to an Env trimer and CD4. CG10 recognized the open Env shape like V2i antibodies but directly contacted CD4 and gp120. Structural similarities of these and previously reported CD4i antibody interactions with Env explain how HIV-1 infection elicits these antibodies. IMPORTANCE RV144 HIV-1 clinical vaccine study indicated limited viral protection. Three further clinical vaccine trials showed that antibody responses to the V1V2 region of HIV-1 Env gp120 were inversely linked with infection risk. In nonhuman monkeys, antibodies targeting V1V2 protect against SIV and SHIV infections. We structurally characterized V2i antibodies against V1V2 from HIV-1-infected patients in combination with open Env trimers linked to CD4. We characterized a CD4i antibody that binds with CD4 and the gp120 subunit of an open Env trimer. Our findings reveals HIV-1 infection produced V2i and CD4i antibodies.

Yang, Z., Dam, K. A., Gershoni, J. M., Zolla-Pazner, S., & Bjorkman, P. J. (2022). Antibody Recognition of CD4-Induced Open HIV-1 Env Trimers. Journal of virology, 96(24), e0108222. https://doi.org/10.1128/jvi.01082-22