Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies | Zendy

Pan-Pan Zhou | Zendy; Han Wang | Zendy; Mengqi Fang | Zendy; Yangyang Li | Zendy; Hua Wang | Zendy; Shasha Shi | Zendy; Zihao Li | Zendy; Jiapeng Wu | Zendy; Xiaoxu Han | Zendy; Xuanling Shi | Zendy; Hong Shang | Zendy; Tongqing Zhou | Zendy; Linqi Zhang | Zendy

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Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies

Author(s) -

Pan-Pan 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.

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