Tan, YueTong, PeiWang, JunyiZhao, LeiLi, JingYu, YangChen, Ying-HuaWang, Ji2017-06-152017Tan, Yue, Pei Tong, Junyi Wang, Lei Zhao, Jing Li, Yang Yu, Ying-Hua Chen, and Ji Wang. 2017. “The Membrane-Proximal Region of C–C Chemokine Receptor Type 5 Participates in the Infection of HIV-1.” Frontiers in Immunology 8 (1): 478. doi:10.3389/fimmu.2017.00478. http://dx.doi.org/10.3389/fimmu.2017.00478.http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029724The initial infection and transmission of HIV-1 requires C–C chemokine receptor type 5 (CCR5). Here, we report that the membrane-proximal region (MPR, aa 22–38) of CCR5 participates in the infection of HIV-1. First, MPR-specific antibodies elicited in mice dose-dependently inhibited the infection of CCR5-tropic HIV-1. Second, substituting MPR with the same region from other co-receptors significantly impaired HIV-1 infection, while the key residues identified by alanine scanning mutagenesis formed an exposed leucine zipper-like structure. Moreover, a peptide derived from MPR could block the infection of a number of HIV-1 strains only before the formation of gp41 six-helix bundle, coincide with the early interaction between CCR5 and the gp120 protein during HIV-1 infection. These promising results ensured the potential of this previously uncharacterized domain as a starting point for the development of antiviral drugs, blocking antibodies, and HIV vaccines.en-USC–C chemokine receptor type 5membrane-proximal regionHIV-1blocking antibodyHIV vaccineJournal Article2017-06-1510.3389/fimmu.2017.00478