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

Wang, Hongye, Yuan, Ting, Li, Tingting, Li, Yanpeng, Qian, Feng, Zhu, Chuanwu, Liang, Shujia, Hoffmann, Daniel, Dittmer, Ulf, Sun, Binlian, Yang, Rongge
Archives of virology 2018 v.163 no.12 pp. 3303-3315
HIV infections, Human immunodeficiency virus 1, Pseudoviridae, binding sites, clones, disease control, mutation, neutralization, neutralization tests, neutralizing antibodies, therapeutics, viruses, China
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.