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Virology . Eight-amino-acid sequence at the N-terminus of SARS-CoV-2 nsp1 is involved in stabilizing viral genome replication

tetano

Editor, Senior Moderator
Virology


. 2024 Apr 8:595:110068.
doi: 10.1016/j.virol.2024.110068. Online ahead of print. Eight-amino-acid sequence at the N-terminus of SARS-CoV-2 nsp1 is involved in stabilizing viral genome replication

Shiori Ueno[SUP] 1 [/SUP], Sodbayasgalan Amarbayasgalan[SUP] 1 [/SUP], Yoshiro Sugiura[SUP] 1 [/SUP], Tatsuki Takahashi[SUP] 1 [/SUP], Kenta Shimizu[SUP] 1 [/SUP], Keisuke Nakagawa[SUP] 2 [/SUP], Reika Kawabata-Iwakawa[SUP] 3 [/SUP], Wataru Kamitani[SUP] 4 [/SUP]



Affiliations
Abstract

Coronavirus disease 19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enveloped virus with a single-stranded positive-sense ribonucleic acid (RNA) genome. The CoV non-structural protein (nsp) 1 is a multifunctional protein that undergoes translation shutoff, messenger RNA (mRNA) cleavage, and RNA binding. The C-terminal region is involved in translational shutoff and RNA cleavage. The N-terminal region of SARS-CoV-2 nsp1 is highly conserved among isolated SARS-CoV-2 variants. However, the I-004 variant, isolated during the early SARS-CoV-2 pandemic, lost eight amino acids in the nsp1 region. In this study, we showed that the eight amino acids are important for viral replication in infected interferon-incompetent cells and that the recombinant virus that lost these amino acids had low pathogenicity in the lungs of hamster models. The loss of eight amino acids-induced mutations occurred in the 5' untranslated region (UTR), suggesting that nsp1 contributes to the stability of the viral genome during replication.

Keywords: 5′ UTR; Coronavirus; Mutations; SARS-CoV-2; nsp1.

 
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