SARS-CoV-2 spreads through cell-to-cell transmission.
SARS-CoV-2 spreads through cell-to-cell transmission.
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DOI：
10.1073/pnas.2111400119
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发表时间：
2022-01-04
影响因子：
11.1
通讯作者：
Liu SL
中科院分区：
文献类型：
--
作者：
Zeng C;Evans JP;King T;Zheng YM;Oltz EM;Whelan SPJ;Saif LJ;Peeples ME;Liu SL
目前尚不清楚 SARS-CoV-2 是否可以通过细胞间接触传播，如果可以，其潜在机制和影响尚不清楚。在这项工作中，我们通过使用慢病毒假型病毒证明，SARS-CoV-2的刺突蛋白介导病毒细胞间传播，其效率高于SARS-CoV。我们还发现细胞间融合有助于细胞间传播，但 ACE2 并不是绝对必需的。虽然受关注的真实变体 (VOC) B.1.1.7（α）和 B.1.351（β）在无细胞感染性方面与野生型以及彼此之间不同，但这些 VOC 具有相似的细胞间传播能力，并且对疫苗接种者血清的中和表现出不同的敏感性。我们的研究结果将有助于更好地了解 SARS-CoV-2 的传播和发病机制。严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是一种高度传播的冠状病毒，是导致全球 COVID-19 大流行的原因。在此，我们提供了证据表明 SARS-CoV-2 在刺突糖蛋白介导下通过培养物中的细胞与细胞接触传播。 SARS-CoV-2 刺突在促进细胞间传播方面比 SARS-CoV 刺突更有效，这在一定程度上反映了它们不同的细胞间融合活性。有趣的是，用内体进入抑制剂处理共培养细胞会损害细胞间的传播，这表明内体膜融合是一种潜在机制。与无细胞感染相比，SARS-CoV-2的细胞间传播难以被中和抗体或COVID-19患者恢复期血清抑制。虽然血管紧张素转换酶 2 可以增强细胞间的传递，但我们发现这并不是绝对必需的。值得注意的是，尽管无细胞感染性存在差异，但真正的受关注变体 (VOC) B.1.1.7（α）和 B.1.351（β）具有相似的细胞间传播能力。此外，B.1.351在无细胞感染中更能抵抗受疫苗者血清的中和，而B.1.1.7在细胞间传播中更能抵抗受疫苗者血清的抑制。总体而言，我们的研究揭示了 SARS-CoV-2 刺突介导的细胞间传播的关键特征，对于更好地了解 SARS-CoV-2 传播和发病机制具有重要意义。
It is currently unknown if SARS-CoV-2 can spread through cell–cell contacts, and if so, the underlying mechanisms and implications. In this work, we show, by using lentiviral pseudotyped virus, that the spike protein of SARS-CoV-2 mediates the viral cell-to-cell transmission, with an efficiency higher than that of SARS-CoV. We also find that cell–cell fusion contributes to cell-to-cell transmission, yet ACE2 is not absolutely required. While the authentic variants of concern (VOCs) B.1.1.7 (alpha) and B.1.351 (beta) differ in cell-free infectivity from wild type and from each other, these VOCs have similar cell-to-cell transmission capability and exhibit differential sensitivity to neutralization by vaccinee sera. Results from our study will contribute to a better understanding of SARS-CoV-2 spread and pathogenesis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein, we provide evidence that SARS-CoV-2 spreads through cell–cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than is SARS-CoV spike, which reflects, in part, their differential cell–cell fusion activity. Interestingly, treatment of cocultured cells with endosomal entry inhibitors impairs cell-to-cell transmission, implicating endosomal membrane fusion as an underlying mechanism. Compared with cell-free infection, cell-to-cell transmission of SARS-CoV-2 is refractory to inhibition by neutralizing antibody or convalescent sera of COVID-19 patients. While angiotensin-converting enzyme 2 enhances cell-to-cell transmission, we find that it is not absolutely required. Notably, despite differences in cell-free infectivity, the authentic variants of concern (VOCs) B.1.1.7 (alpha) and B.1.351 (beta) have similar cell-to-cell transmission capability. Moreover, B.1.351 is more resistant to neutralization by vaccinee sera in cell-free infection, whereas B.1.1.7 is more resistant to inhibition by vaccinee sera in cell-to-cell transmission. Overall, our study reveals critical features of SARS-CoV-2 spike-mediated cell-to-cell transmission, with important implications for a better understanding of SARS-CoV-2 spread and pathogenesis.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
DOI：
10.4049/jimmunol.2000583
发表时间：
2020-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Alsoussi WB;Turner JS;Case JB;Zhao H;Schmitz AJ;Zhou JQ;Chen RE;Lei T;Rizk AA;McIntire KM;Winkler ES;Fox JM;Kafai NM;Thackray LB;Hassan AO;Amanat F;Krammer F;Watson CT;Kleinstein SH;Fremont DH;Diamond MS;Ellebedy AH
通讯作者：
Ellebedy AH
DOI：
10.1038/s41577-021-00522-1
发表时间：
2021-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Carvalho T;Krammer F;Iwasaki A
通讯作者：
Iwasaki A
影响因子：
64.5
作者：
Grubaugh ND;Hodcroft EB;Fauver JR;Phelan AL;Cevik M
通讯作者：
Cevik M
影响因子：
11.8
作者：
Banerjee, Arinjay;Nasir, Jalees A.;Mubareka, Samira
通讯作者：
Mubareka, Samira