title: The potent human immunodeficiency virus type 1 (HIV-1) entry inhibitor HR212 blocks formation of the envelope glycoprotein gp41 six-helix bundle.
abstract: HR212, a recombinant protein composed of the heptad repeat, is a rationally designed human immunodeficiency virus type 1 (HIV-1) fusion inhibitor. This protein can be easily produced by Escherichia coli at a low cost. Previously, studies indicated that HR212 can efficiently inhibit the entry and replication of both laboratory and clinical HIV-1 strains, and this protein is more stable and less sensitive to proteinases than T20. The procedure of HIV-1 entry into the host cells can be divided into three main steps: gp120-CD4 interactions, coreceptor binding, and gp41 six-helix bundle formation and subsequent membrane fusion. The present study demonstrates that HR212 does not block gp120-CD4 binding or interfere with binding to the coreceptors CXCR4 and CCR5. Instead, HR212 efficiently blocks the six-helix bundle formation between peptides derived from the N-terminal heptad repeat (NHR) and the C-terminal heptad repeat (CHR) region of gp41. Fluorescence native polyacrylamide gel electrophoresis (FN-PAGE) indicated that HR212 could form a complex with peptide N36 to block gp41 fusogenic core formation. These results suggest that HR212 inhibits HIV-1 entry by targeting the NHR region of gp41. Therefore, HR212 can potentially be developed as a novel, high-efficiency, specific HIV-1 entry inhibitor.
authors: State Key Laboratory of Virology and Modern Virology Research Center, The College of Life Sciences, Wuhan University, Wuhan, China.
authors: Wenjie
authors: W
authors: Ouyang
authors: Tai
authors: T
authors: An
authors: Deyin
authors: D
authors: Guo
authors: Shuwen
authors: S
authors: Wu
authors: Po
authors: P
authors: Tien
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011485:Protein Binding; D017510:Protein Folding / Q000187:drug effects*
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; C514787:gp41 protein, Human immunodeficiency virus 1