Обзор посвящен критическому анализу известных исследований вируса SARS-CoV-2, вызвавшего самую масштабную эпидемию XXI в., позволивших, с высокой степенью вероятности, описать биогенез вируса. SARS-CoV-2 проникает в клетку путем клатрин-зависимого эндоцитоза. В эндосоме S-белок SARS-CoV-2 расщепляется с помощью TMDRSS2, и образовавшаяся S2-субъединица перфорирует мембраны эндосом, в результате чего его +РНК оказывается в цитозоле. Вирус вызывает в клетке образование органеллы вирусной репликации, состоящей из сети замкнутых мембран эндоплазматического ретикулюма и двухмембранных вакуолей (ДМВ), где он генерирует репликационную вилку. ДМВ образуются из мембран эндоплазматического ретикулюма с ключевым участием белка NSP6 и содержат дцРНК вируса. Через поры ДМВ дцРНК может выходить в цитозоль. Из репликационной органеллы вирус доставляется к комплексу Гольджи, транспортируется через него, после чего белки вируса становятся высоко гликозилированными. Вирионы концентрируются в пост-Гольджи переносчиках, которыми они доставляются к плазмалемме инфицированной клетки и сливаются с ней, высвобождая вирус в просвет дыхательных путей. Ключевые механизмы биогенеза изучены, однако остается много неясных моментов, понимание которых поможет в лечении и профилактике инфекции.
This review presents itself as a critical analysis of the well-known studies of the SARS-CoV-2 virus, which caused the largest epidemic of the 21st century, making it possible with a high degree of probability to describe the biogenesis of the virus. SARS-CoV-2 enters the cell by clathrin-dependent endocytosis. In the endosome, the SARS-CoV-2 S protein is cleaved by TMDRSS2, and the resulting S2 subunit perforates the endosome membranes, that allows its +RNA to enter the cytosol. The virus causes the formation of a viral replication organelle in the cell, which consists of a network of closed membranes of the endoplasmic reticulum and double-membrane vacuoles (DMV), where it generates a replication fork. DMV are formed from the membranes of the endoplasmic reticulum with the key participation of the NSP6 protein and contain the dsRNA of the virus. Through the pores of the DMV, dsRNA can enter the cytosol. From the replication organelle, the virus is then delivered to the Golgi complex, transported through it, after which the viral proteins become highly glycosylated. Virions are concentrated in post-Golgi carriers, that deliver them to the plasmalemma of an infected cell and merge with it, releasing the virus into the airways of the body. The key mechanisms of biogenesis have been studied, but many unclear points still remain, the understanding of which will help in the treatment and prevention of the infection.
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