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Review
. 2021 Sep 28:12:752214.
doi: 10.3389/fmicb.2021.752214. eCollection 2021.

Coronavirus Nsp1: Immune Response Suppression and Protein Expression Inhibition

Shuai Yuan  1 , Shravani Balaji  1 , Ivan B Lomakin  2 , Yong Xiong  1
Affiliations
Review

Coronavirus Nsp1: Immune Response Suppression and Protein Expression Inhibition

Shuai Yuan et al. Front Microbiol. .

Abstract

Coronaviruses have brought severe challenges to public health all over the world in the past 20years. SARS-CoV-2, the causative agent of the COVID-19 pandemic that has led to millions of deaths, belongs to the genus beta-coronavirus. Alpha- and beta-coronaviruses encode a unique protein, nonstructural protein 1 (Nsp1) that both suppresses host immune responses and reduces global gene expression levels in the host cells. As a key pathogenicity factor of coronaviruses, Nsp1 redirects the host translation machinery to increase synthesis of viral proteins. Through multiple mechanisms, coronaviruses impede host protein expression through Nsp1, while escaping inhibition to allow the translation of viral RNA. In this review, we discuss current data about suppression of the immune responses and inhibition of protein synthesis induced by coronavirus Nsp1, as well as the prospect of live-attenuated vaccine development with virulence-attenuated viruses with mutations in Nsp1.

Keywords: coronavirus; immune suppression; nonstructural protein 1; translation inhibition; vaccine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Steps of the innate immune response pathways that potentially be suppressed by nonstructural protein 1 (Nsp1). Key steps that are found inhibited by Nsp1 are labeled.
Figure 2
Figure 2
Sequence analysis of Nsp1 from severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), transmissible gastroenteritis virus (TGEV), HCoV-229E, and HCoV-NL63. Key conserved residues in SARS-CoV, SARS-CoV-2, and MERS-CoV are labeled with the blue boxes. Conserved residues are labeled in red boxes and shades.
Figure 3
Figure 3
Crystal structures of Nsp1 of SARS-CoV (PDB: 2HSX), SARS-CoV-2 (PDB: 7K7P), and TGEV (PDB: 3ZBD) shown in cartoon. Rainbow coloring from blue to red indicates the N- to C-terminal positions of the residues in the model.
Figure 4
Figure 4
Cryo-EM structure of the Nsp1 C-terminal region-40S ribosomal subunit complex, with Nsp1 (red surface) and the surrounding protein uS3 (cyan sphere representation), uS5 (magenta) and rRNA h18 (green) highlighted. The inset shows zoomed-in view of Nsp1 in cartoon, with the surrounding 40S components in cartoon and surface to illustrate the mRNA entry channel.
See this image and copyright information in PMC

References

    1. Akira S., Uematsu S., Takeuchi O. (2006). Pathogen recognition and innate immunity. Cell 124, 783–801. doi: 10.1016/j.cell.2006.02.015, PMID: - DOI - PubMed
    1. Alexopoulou L., Holt A. C., Medzhitov R., Flavell R. A. (2001). Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature 413, 732–738. doi: 10.1038/35099560, PMID: - DOI - PubMed
    1. Almeida M. S., Johnson M. A., Herrmann T., Geralt M., Wuthrich K. (2007). Novel beta-barrel fold in the nuclear magnetic resonance structure of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus. J. Virol. 81, 3151–3161. doi: 10.1128/JVI.01939-06, PMID: - DOI - PMC - PubMed
    1. Aylett C. H., Boehringer D., Erzberger J. P., Schaefer T., Ban N. (2015). Structure of a yeast 40S-eIF1-eIF1A-eIF3-eIF3j initiation complex. Nat. Struct. Mol. Biol. 22, 269–271. doi: 10.1038/nsmb.2963, PMID: - DOI - PubMed
    1. Babaylova E., Malygin A., Gopanenko A., Graifer D., Karpova G. (2019). Tetrapeptide 60–63 of human ribosomal protein uS3 is crucial for translation initiation. Biochim. Biophys. Acta 1862:194411. doi: 10.1016/j.bbagrm.2019.194411, PMID: - DOI - PubMed