Isolation of SARS-CoV-2 strains carrying a nucleotide mutation, leading to a stop codon in the ORF 6 protein

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was isolated from the oro/pharyngeal swabs of two Italian COVID-19 patients, physicians in a COVID-19 division hospital, with different courses of the disease. The complete genome sequences show that the two isolates belong to the B1.1 lineage, but contain a nucleotide mutation in the ORF6, leading to a stop codon and to the deletion of 6 amino acids in the C terminus. This deletion was unique, compared to the currently available sequences deposited in the GISAID and GenBank database. It did not affect the in vitro viral replication, neither the neutralizing activities of the patients' antibodies. Based on homology analysis with other Coronaviruses, the two isolated lacked the ORF6 aminoacidic portion responsible for the inhibition of the antiviral Interferon (IFN)-based host response. IFN seems to have a dual role of in SARS-CoV-2 infected patients: not only antiviral activity, but also a detrimental role in case of excessive production. A deletion in the SARS-CoV-2 ORF6 protein might have a specific, still unknown role in the viral pathogenesis.

研究从两名意大利新冠患者的口咽拭子中分离出严重急性呼吸综合征冠状病毒2（SARS-CoV-2），两名患者均为某新冠专科病房医院的医师，二人病情进程存在显著差异。全基因组序列分析显示，两株分离毒株均隶属于B.1.1进化分支，但在开放阅读框6（ORF6）区域存在一处核苷酸突变，该突变引入终止密码子，致使病毒蛋白C端缺失6个氨基酸残基。与目前已提交至GISAID及GenBank数据库的所有现有序列相比，该缺失突变为独特变异。该突变既未影响病毒的体外复制活性，也未改变患者抗体的中和活性。通过与其他冠状病毒进行同源性分析可知，这两株分离毒株缺失了ORF6蛋白中负责抑制基于干扰素（Interferon，IFN）的宿主抗病毒免疫应答的氨基酸区段。干扰素在新冠病毒感染患者体内呈现双重作用：不仅可发挥抗病毒功效，当机体过量产生干扰素时，还可能产生有害影响。新冠病毒ORF6蛋白的该缺失突变，可能在病毒致病机制中发挥尚未明确的特定作用。