Identification and differential usage of a host metalloproteinase entry pathway by SARS-CoV-2 Delta and Omicron.
Identification and differential usage of a host metalloproteinase entry pathway by SARS-CoV-2 Delta and Omicron.
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DOI：
10.1016/j.isci.2022.105316
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发表时间：
2022-11-18
期刊：
影响因子：
5.8
通讯作者：
Cote, Marceline
中科院分区：
文献类型：
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作者：
Benlarbi, Mehdi;Laroche, Genevieve;Fink, Corby;Fu, Kathy;Mulloy, Rory P.;Phan, Alexandra;Ariana, Ardeshir;Stewart, Corina M.;Prevost, Jeremie;Beaudoin-Bussieres, Guillaume;Daniel, Redaet;Bo, Yuxia;El Ferri, Omar;Yockell-Lelievre, Julien;Stanford, William L.;Giguere, Patrick M.;Mubareka, Samira;Finzi, Andres;Dekaban, Gregory A.;Dikeakos, Jimmy D.;Cote, Marceline
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）刺突糖蛋白（S）与血管紧张素转换酶2（ACE 2）结合，通过两种不同的途径介导膜融合：1）表面丝氨酸蛋白酶依赖性途径或2）内体半胱氨酸蛋白酶依赖性途径。在本研究中，我们发现SARS-CoV-2S具有更广泛的蛋白酶用途，并且还可以被TMPRSS 13和基质金属蛋白酶（MMPs）激活。我们发现MMP-2和MMP-9在SARS-CoV-2S细胞-细胞融合以及高表达MMP水平的细胞中的TMPRSS 2和组织蛋白酶非依赖性病毒进入中发挥作用。MMP依赖性病毒进入需要在病毒生产细胞中的S1/S2连接处裂解，并且关注S的变体的差异加工决定了其使用;有效加工的Delta S在可用时优选金属蛋白酶依赖性进入，并且较少加工的Omicron S不能使用金属蛋白酶进入。由于MMP-2/9在炎症过程中释放，它们可能在S介导的细胞病变效应、向性和疾病结局中发挥作用。MMP-2和MMP-9使SARS-CoV-2 S-介导的合胞体在缺乏TMPRSS 2的情况下成为可能SARS-CoV-2可以通过MMP以TMPRSS 2和组织蛋白酶非依赖性方式进入细胞MMP依赖性S激活需要先进行S1/S2处理Delta S可以容易地使用MMP进入，而Omicron S不能生物科学;分子生物学;微生物学;病毒学
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike glycoprotein (S) binds to angiotensin-converting enzyme 2 (ACE2) to mediate membrane fusion via two distinct pathways: 1) a surface, serine protease-dependent or 2) an endosomal, cysteine protease-dependent pathway. In this study, we found that SARS-CoV-2 S has a wider protease usage and can also be activated by TMPRSS13 and matrix metalloproteinases (MMPs). We found that MMP-2 and MMP-9 played roles in SARS-CoV-2 S cell-cell fusion and TMPRSS2- and cathepsin-independent viral entry in cells expressing high MMP levels. MMP-dependent viral entry required cleavage at the S1/S2 junction in viral producer cells, and differential processing of variants of concern S dictated its usage; the efficiently processed Delta S preferred metalloproteinase-dependent entry when available, and less processed Omicron S was unable to us metalloproteinases for entry. As MMP-2/9 are released during inflammation, they may play roles in S-mediated cytopathic effects, tropism, and disease outcome. MMP-2 and MMP-9 enable SARS-CoV-2 S-mediated syncytia in the absence of TMPRSS2 SARS-CoV-2 can enter cells via MMPs in a TMPRSS2- and cathepsin-independent manner MMP-dependent S activation requires prior S1/S2 processing Delta S can readily use MMPs for entry while Omicron S cannot Biological sciences; Molecular biology; Microbiology; Virology
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影响因子：
5.4
作者：
Heurich, Adeline;Hofmann-Winkler, Heike;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
DOI：
10.1016/j.biopha.2021.112067
发表时间：
2021-10
期刊：
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子：
--
作者：
D Avila-Mesquita C;Couto AES;Campos LCB;Vasconcelos TF;Michelon-Barbosa J;Corsi CAC;Mestriner F;Petroski-Moraes BC;Garbellini-Diab MJ;Couto DMS;Jordani MC;Ferro D;Sbragia L;Joviliano EE;Evora PR;Carvalho Santana R;Martins-Filho OA;Polonis K;Menegueti MG;Ribeiro MS;Auxiliadora-Martins M;Becari C
通讯作者：
Becari C
影响因子：
5.3
作者：
Carter-Timofte, Madalina Elena;Arulanandam, Rozanne;Olagnier, David
通讯作者：
Olagnier, David
影响因子：
9.9
作者：
Hikmet, Feria;Mear, Loren;Lindskog, Cecilia
通讯作者：
Lindskog, Cecilia