THETA: a new genotypic approach for predicting HIV-1 CRF02-AG coreceptor usage
BIOINFORMATICS
Authors: Dimeglio, Chloe; Raymond, Stephanie; Jeanne, Nicolas; Reynes, Christelle; Carcenac, Romain; Lefebvre, Caroline; Cazabat, Michelle; Nicot, Florence; Delobel, Pierre; Izopet, Jacques
Abstract
Motivation: The circulating recombinant form of HIV-1 CRF02-AG is the most frequent non-B subtype in Europe. Anti-HIV therapy and pathophysiological studies on the impact of HIV-1 tropism require genotypic determination of HIV-1 tropism for non-B subtypes. But genotypic approaches based on analysis of the V3 envelope region perform poorly when used to determine the tropism of CRF02-AG. We, therefore, designed an algorithm based on information from the gp120 and gp41 ectodomain that better predicts the tropism of HIV-1 subtype CRF02-AG. Results: We used a bio-statistical method to identify the genotypic determinants of CRF02-AG core-ceptor use. Toulouse HIV Extended Tropism Algorithm (THETA), based on a Least Absolute Shrinkage and Selection Operator method, uses HIV envelope sequence from phenotypically characterized clones. Prediction of R5X4/X4 viruses was 86% sensitive and that of R5 viruses was 89% specific with our model. The overall accuracy of THETA was 88%, making it sufficiently reliable for predicting the tropism of subtype CRF02-AG sequences.
The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity
CELL
Authors: Li, Qianqian; Wu, Jiajing; Nie, Jianhui; Zhang, Li; Hao, Huan; Liu, Shuo; Zhao, Chenyan; Zhang, Qi; Liu, Huan; Nie, Lingling; Qin, Haiyang; Wang, Meng; Lu, Qiong; Li, Xiaoyu; Sun, Qiyu; Liu, Junkai; Zhang, Linqi; Li, Xuguang; Huang, Weijin; Wang, Youchun
Abstract
The spike protein of SARS-CoV-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here, we investigated 80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious, but variants including A475V, L452R, V483A, and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious, whereas deletion of both N331 and N343 glycosylation drastically reduced infectivity, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in the development of vaccine and therapeutic antibodies.