Open AccessBroadly resistant HIV-1 against CD4-binding site neutralizing antibodies
Author(s) -
Panpan Zhou,
Han Wang,
Mengqi Fang,
Yangyang Li,
Hua Wang,
Shasha Shi,
Zihao Li,
Jiapeng Wu,
Xiaoxu Han,
Xuanling Shi,
Hong Shang,
Tongqing Zhou,
Linqi Zhang
Publication year - 2019
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1007819
Subject(s) - virology , biology , epitope , antibody , human immunodeficiency virus (hiv) , mutagenesis , neutralizing antibody , binding site , virus , mutation , immunology , genetics , gene
Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection. However, resistant strains may impose substantial challenges. Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4-binding site (CD4bs). Site-directed mutagenesis revealed that several key epitope mutations facilitate resistance and are located in the inner domain, loop D, and β23/loop V5/β24 of HIV-1 gp120. The resistance is largely correlated with binding affinity of antibodies to the envelope trimers expressed on the cell surface. Our results therefore demonstrate the existence of broadly resistant HIV-1 strains against CD4bs neutralizing antibodies. Treatment strategies based on the CD4bs bnAbs must overcome such resistance to achieve optimal clinical outcomes.