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Evaluation of susceptibility of HIV-1 CRF01_AE variants to neutralization by a panel of broadly neutralizing antibodies

Author:
Wang, Hongye, Yuan, Ting, Li, Tingting, Li, Yanpeng, Qian, Feng, Zhu, Chuanwu, Liang, Shujia, Hoffmann, Daniel, Dittmer, Ulf, Sun, Binlian, Yang, Rongge
Source:
Archives of virology 2018 v.163 no.12 pp. 3303-3315
ISSN:
0304-8608
Subject:
HIV infections, Human immunodeficiency virus 1, Pseudoviridae, binding sites, clones, disease control, mutation, neutralization, neutralization tests, neutralizing antibodies, therapeutics, viruses, China
Abstract:
Broadly neutralizing antibodies (bNAbs) are very promising agents for HIV-1 prophylaxis and AIDS treatment. However, the neutralization susceptibility of circulating recombinants such as CRF01_AE, which is becoming increasingly prevalent, has not been studied in detail until now. Here, we focused on CRF01_AE in China and aimed to find bNAbs that can be used for neutralization of CRF01_AE. Full-length env clones were obtained from the plasma samples of 22 HIV-1-infected individuals sampled in 2009 and 2015. An env-pseudovirus-based neutralization assay was conducted using five categories of bNAbs: VRC01, NIH45-46ᴳ⁵⁴ᵂ, and 3BNC117 (targeting the CD4 binding site); PG9 and PG16 (targeting the V1V2 loop); 2G12 (glycan specific), PGT121 and 10-1074 (targeting the V3 glycan); 2F5, 4E10, and 10E8 (targeting the membrane-proximal external region (MPER)). The neutralizing efficiency was compared, and features of the escape pseudoviruses were analyzed. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46ᴳ⁵⁴ᵂ and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46ᴳ⁵⁴ᵂand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. Our results may help for choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.
Agid:
6206911