新冠病毒非结构蛋白氨基酸变异与疾病严重程度的关系探究  

Study on the relationship between amino acid variation of novel coronavirus non-structural protein and disease severity

作　　者：边紫薇 李东 黄小丽 徐映华 王茜 刘书洁 胡贵方[1] 王海鹰 BIAN Zi-wei;LI Dong;HUANG Xiao-li;XU Ying-hua;WANG Qian;LIU Shu-jie;HU Gui-fang;WANG Hai-ying(Department of Epidemiology,School of Public Health,Southern Medical University,Guangzhou,Guangdong 510515,China)

机构地区：[1]南方医科大学公共卫生学院流行病学系,广东广州510515

出　　处：《现代预防医学》2024年第11期2094-2099,共6页Modern Preventive Medicine

基　　金：国家自然科学基金青年科学基金(31800146)。

摘　　要：目的本研究旨在探讨严重急性呼吸综合征冠状病毒2型(severe acute respiratory syndrome corona coronavirus 2,SARS-CoV-2)非结构蛋白氨基酸变异是否与新型冠状病毒感染(corona virus disease 2019,COVID-19)疾病严重程度有关。方法对全球共享流感数据倡议组织(GISAID)数据库得到的数据进行分析,筛选SARS-CoV-2序列中突变频率较高的非结构蛋白氨基酸突变。将患者结果分为轻症和重症,采用χ^(2)检验比较组间基线特征,逻辑回归检验选择的突变与患者预后之间的关系。结果共纳入数据23498例,其中男性11444例(48.70%),女性12054例(51.30%),中位数年龄[M(P_(25),P_(75))]为38(26,53)岁。男性新冠病毒感染重症率高于女性(χ^(2)=226.564,P<0.001);随着年龄增加(χ^(2)=6088.032,P<0.001),新冠病毒感染重症率增加。发病年份(χ^(2)=1604.070,P<0.001)、大洲(χ^(2)=4520.240,P<0.001)与新冠病毒感染严重程度显著相关。确定了SARS-CoV-2基因组中几种可能与新冠病毒感染严重程度相关的氨基酸变异,NSP4_T492I(aOR=0.574,95%CI:0.487~0.676)、NSP12_G671S(aOR=0.657,95%CI:0.458~0.941)、NSP6_T77A(aOR=0.422,95%CI:0.235~0.759)、NSP3_P1228L(aOR=0.124,95%CI:0.080~0.190)与新冠病毒感染重症呈负相关,而NSP12_P323L(aOR=2.126,95%CI:1.531~2.953)、NSP13_P77L(aOR=1.923,95%CI:1.115~2.369)、NSP14_A394V(aOR=20.486,95%CI:9.649~43.495)与新冠病毒感染重症呈正相关。结论SARS-CoV-2非结构蛋白氨基酸变异可能与新冠病毒感染严重程度相关,需要进一步验证筛选可能与新冠病毒感染严重程度相关的非结构蛋白氨基酸变异。Objective To investigate whether the amino acid variation in the nonstructural protein of Severe Acute Respiratory Syndrome Coronavirus2(SARS-CoV-2)is related to the severity of Corona Virus Disease 2019(COVID-19).Methods The data obtained from the Global Shared Influenza Data Initiative(GISAID)database were analyzed,and the nonstructural protein amino acid mutations with high mutation rate in SARS-CoV-2 sequences were screened.The outcomes were divided into mild and severe diseases,and the chi-square test was used to compare the basic characteristics between the groups.The relationship between the mutations selected and the prognosis of the patients was analyzed.Results A total of 23498 cases were included,including 11444 males(48.70%)and 12054 females(51.30%).The median age[M(P25,P_(75))]was 38(26-53)years old.The severe infection rate of novel coronavirus in male was higher than that in female(χ^(2)=226.564,P<0.001).The severe infection rate of novel coronavirus increased with the increase of age(χ^(2)=6088.032,P<0.001).The year of onset(χ^(2)=1604.070,P<0.001)and continent(χ^(2)=4520.240,P<0.001)were significantly correlated with the severity of novel corona virus infection.Several amino acid variations in the SARS-CoV-2 gene group associated with the severity of novel corona virus’s sensitive dyeing were determined.NSP4_T492I(aOR=0.574,95%CI:0.487-0.676),NSP12_G671S(aOR=0.657,95%CI:0.458-0.941),NSP6_T77A(aOR=0.422,95%CI:0.235-0.759),and NSP3_P1228L(aOR=0.124,95%CI:0.080-0.190)were negatively correlated with novel coronavirus’s severe infection.NSP12_P323L(aOR=2.126,95%CI:1.531-2.953),NSP13_P77L(aOR=1.923,95%CI:1.115-2.369),and NSP14_A394V(aOR=20.486,95%CI:9.649-43.495)were positively correlated with novel coronavirus’s severe infection.Conclusion The amino acid variation of SARS-CoV-2 nonstructural protein may be related to the severity of COVID-19 virus infection,and it is necessary to screen several nonstructural protein amino acid variants which can be related to the severity of novel coronaviru

关 键 词：SARS-CoV-2 疾病严重程度 氨基酸变异 非结构蛋白 新冠病毒感染 

分 类 号：R373.1[医药卫生—病原生物学]