Dataset Information

Host and viral determinants for efficient SARS-CoV-2 infection of the human lung.

ABSTRACT: Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.

SUBMITTER: Chu H

PROVIDER: S-EPMC7794309 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Host and viral determinants for efficient SARS-CoV-2 infection of the human lung.

Chu Hin H Hu Bingjie B Huang Xiner X Chai Yue Y Zhou Dongyan D Wang Yixin Y Shuai Huiping H Yang Dong D Hou Yuxin Y Zhang Xi X Yuen Terrence Tsz-Tai TT Cai Jian-Piao JP Zhang Anna Jinxia AJ Zhou Jie J Yuan Shuofeng S To Kelvin Kai-Wang KK Chan Ivy Hau-Yee IH Sit Ko-Yung KY Foo Dominic Chi-Chung DC Wong Ian Yu-Hong IY Ng Ada Tsui-Lin AT Cheung Tan To TT Law Simon Ying-Kit SY Au Wing-Kuk WK Brindley Melinda A MA Chen Zhiwei Z Kok Kin-Hang KH Chan Jasper Fuk-Woo JF Yuen Kwok-Yung KY

Nature communications 20210108 1

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent e ...[more]

PMID: 33420022

Similar Datasets

Project description:Coronaviruses are commonly characterized by a unique discontinuous RNA transcriptional synthesis strategy guided by transcription-regulating sequences (TRSs). However, the details of RNA synthesis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. Here, we present a time-scaled, gene-comparable transcriptome of SARS-CoV-2, demonstrating that ACGAAC functions as a core TRS guiding the discontinuous RNA synthesis of SARS-CoV-2 from a holistic perspective. During infection, viral transcription, rather than genome replication, dominates all viral RNA synthesis activities. The most highly expressed viral gene is the nucleocapsid gene, followed by ORF7 and ORF3 genes, while the envelope gene shows the lowest expression. Host transcription dysregulation keeps exacerbating after viral RNA synthesis reaches a maximum. The most enriched host pathways are metabolism related. Two of them (cholesterol and valine metabolism) affect viral replication in reverse. Furthermore, the activation of numerous cytokines emerges before large-scale viral RNA synthesis. IMPORTANCE SARS-CoV-2 is responsible for the current severe global health emergency that began at the end of 2019. Although the universal transcriptional strategies of coronaviruses are preliminarily understood, the details of RNA synthesis, especially the time-matched transcription level of each SARS-CoV-2 gene and the principles of subgenomic mRNA synthesis, are not clear. The coterminal subgenomic mRNAs of SARS-CoV-2 present obstacles in identifying the expression of most genes by PCR-based methods, which are exacerbated by the lack of related antibodies. Moreover, SARS-CoV-2-related metabolic imbalance and cytokine storm are receiving increasing attention from both clinical and mechanistic perspectives. Our transcriptomic research provides information on both viral RNA synthesis and host responses, in which the transcription-regulating sequences and transcription levels of viral genes are demonstrated, and the metabolic dysregulation and cytokine levels identified at the host cellular level support the development of novel medical treatment strategies.

Dataset Information

Host and viral determinants for efficient SARS-CoV-2 infection of the human lung.

Publications

Host and viral determinants for efficient SARS-CoV-2 infection of the human lung.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets