新型冠状病毒(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引发了全球大流行的新型冠状病毒感染(Coronavirusdisease 2019,COVID-19),对人类健康和社会经济发展造成极大威胁,深入研究其感染复制机制对防控该病毒致病及流行至关重要.有研究发现SARS-CoV-2可通过网格蛋白介导的内吞、转运系统进入细胞建立感染.衔接蛋白复合物1 γ1亚基(Adaptor related protein complex 1 subunit gamma 1,AP1G1)是衔接蛋白复合物1(Adapter protein 1,AP-1)的重要组成部分,参与胞吞、囊泡转运等生理过程.本文基于相关文献报道选择AP1G1展开研究,确证其对SARS-CoV-2感染性的影响并初探机制.首先借鉴文献,建立了 SARS-CoV-2病毒样颗粒(SARS-CoV-2 virus like particles,SC2-VLPs)系统作为报告病毒,发现过表达AP1G1降低以携带萤火虫荧光素酶为报告基因的SC2-VLPs-Luc的感染性;敲减内源AP1G1增强SC2-VLPs-Luc的感染性;发现AP1G1可被包装入SC2-VLPs-Luc,虽未改变SC2-VLPs-Luc中病毒结构蛋白组成,但影响SC2-VLPs-Luc递送mRNA能力.本研究为解析AP1G1功能及其对SARS-CoV-2感染性的影响提供了新的实验证据.
Impact of Adaptor-related Protein Complex 1 Subunit Gamma 1 on SARS-CoV-2 Infectivity
In 2020,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)triggered a global pandemic of severe pneumonia known as coronavirus disease 2019(COVID-19).This pandemic posed a great threat to human health and socio-economic development.In-depth research on the infection and replication mechanisms of SARS-CoV-2 is crucial for preventing and controlling its pathogenicity and spread.Studies have found that SARS-CoV-2 can enter cells through the endocytosis and transport system mediated by a grid protein,thereby establishing infection.Adaptor-related protein complex 1 subunit gamma 1(AP1G1)is an important component of adapter protein 1(AP-1)and is involved in phagocytosis and vesicle transport.Based on relevant literature reports,we selected AP1G1 for research to ascertain its impact on SARS-CoV-2 infectivity and to explore its mechanism of action.First,a SARS-CoV-2 virus-like particles(SC2-VLPs)system was established as a reporter virus according to the literature.We found that AP1G1 overexpression reduced,whereas knockdown of expression of endogenous AP1G1 enhanced,the infectivity of SC2-VLPs-Luc.AP1G1 could be packaged into SC2-VLPs-Luc.Though it did not change the composition of the structural protein in SC2-VLPs-Luc,it did affect the mRNA-delivery capacity of SC2-VLPs-Luc.Our study provides new experimental evidence for understanding the function of AP1G1 and its impact on SARS-CoV-2 infectivity.
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