tetano
Editor, Senior Moderator
Virus Evol
. 2022 Nov 29;8(2):veac106.
doi: 10.1093/ve/veac106. eCollection 2022.
SARS-CoV-2 intra-host single-nucleotide variants associated with disease severity
Yi Zhang[SUP] 1 [/SUP], Ning Jiang[SUP] 1 2 [/SUP], Weiqiang Qi[SUP] 3 [/SUP], Tao Li[SUP] 3 [/SUP], Yumeng Zhang[SUP] 1 [/SUP], Jing Wu[SUP] 1 [/SUP], Haocheng Zhang[SUP] 1 [/SUP], Mingzhe Zhou[SUP] 1 [/SUP], Peng Cui[SUP] 1 [/SUP], Tong Yu[SUP] 1 [/SUP], Zhangfan Fu[SUP] 1 [/SUP], Yang Zhou[SUP] 1 [/SUP], Ke Lin[SUP] 1 [/SUP], Hongyu Wang[SUP] 1 [/SUP], Tongqing Wei[SUP] 2 [/SUP], Zhaoqin Zhu[SUP] 3 1 [/SUP], Jingwen Ai[SUP] 1 [/SUP], Chao Qiu[SUP] 1 [/SUP], Wenhong Zhang[SUP] 1 2 [/SUP]
Affiliations
Abstract
Variants of severe acute respiratory syndrome coronavirus 2 frequently arise within infected individuals. Here, we explored the level and pattern of intra-host viral diversity in association with disease severity. Then, we analyzed information underlying these nucleotide changes to infer the impetus including mutational signatures and immune selection from neutralizing antibody or T-cell recognition. From 23 January to 31 March 2020, a set of cross-sectional samples were collected from individuals with homogeneous founder virus regardless of disease severity. Intra-host single-nucleotide variants (iSNVs) were enumerated using deep sequencing. Human leukocyte antigen (HLA) alleles were genotyped by Sanger sequencing. Medical records were collected and reviewed by attending physicians. A total of 836 iSNVs (3-106 per sample) were identified and distributed in a highly individualized pattern. The number of iSNVs paced with infection duration peaked within days and declined thereafter. These iSNVs did not stochastically arise due to a strong bias toward C > U/G > A and U > C/A > G substitutions in reciprocal proportion with escalating disease severity. Eight nonsynonymous iSNVs in the receptor-binding domain could escape from neutralization, and eighteen iSNVs were significantly associated with specific HLA alleles. The level and pattern of iSNVs reflect the in vivo viral-host interaction and the disease pathogenesis.
Keywords: COVID-19; HLA; SARS-CoV-2 variants; immune response; intra-host; neutralization antibody.
. 2022 Nov 29;8(2):veac106.
doi: 10.1093/ve/veac106. eCollection 2022.
SARS-CoV-2 intra-host single-nucleotide variants associated with disease severity
Yi Zhang[SUP] 1 [/SUP], Ning Jiang[SUP] 1 2 [/SUP], Weiqiang Qi[SUP] 3 [/SUP], Tao Li[SUP] 3 [/SUP], Yumeng Zhang[SUP] 1 [/SUP], Jing Wu[SUP] 1 [/SUP], Haocheng Zhang[SUP] 1 [/SUP], Mingzhe Zhou[SUP] 1 [/SUP], Peng Cui[SUP] 1 [/SUP], Tong Yu[SUP] 1 [/SUP], Zhangfan Fu[SUP] 1 [/SUP], Yang Zhou[SUP] 1 [/SUP], Ke Lin[SUP] 1 [/SUP], Hongyu Wang[SUP] 1 [/SUP], Tongqing Wei[SUP] 2 [/SUP], Zhaoqin Zhu[SUP] 3 1 [/SUP], Jingwen Ai[SUP] 1 [/SUP], Chao Qiu[SUP] 1 [/SUP], Wenhong Zhang[SUP] 1 2 [/SUP]
Affiliations
- PMID: 36505092
- PMCID: PMC9728387
- DOI: 10.1093/ve/veac106
Abstract
Variants of severe acute respiratory syndrome coronavirus 2 frequently arise within infected individuals. Here, we explored the level and pattern of intra-host viral diversity in association with disease severity. Then, we analyzed information underlying these nucleotide changes to infer the impetus including mutational signatures and immune selection from neutralizing antibody or T-cell recognition. From 23 January to 31 March 2020, a set of cross-sectional samples were collected from individuals with homogeneous founder virus regardless of disease severity. Intra-host single-nucleotide variants (iSNVs) were enumerated using deep sequencing. Human leukocyte antigen (HLA) alleles were genotyped by Sanger sequencing. Medical records were collected and reviewed by attending physicians. A total of 836 iSNVs (3-106 per sample) were identified and distributed in a highly individualized pattern. The number of iSNVs paced with infection duration peaked within days and declined thereafter. These iSNVs did not stochastically arise due to a strong bias toward C > U/G > A and U > C/A > G substitutions in reciprocal proportion with escalating disease severity. Eight nonsynonymous iSNVs in the receptor-binding domain could escape from neutralization, and eighteen iSNVs were significantly associated with specific HLA alleles. The level and pattern of iSNVs reflect the in vivo viral-host interaction and the disease pathogenesis.
Keywords: COVID-19; HLA; SARS-CoV-2 variants; immune response; intra-host; neutralization antibody.