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

Shiori Ueno; Sodbayasgalan Amarbayasgalan; Yoshiro Sugiura; Tatsuki Takahashi; Kenta Shimizu; Keisuke Nakagawa; Reika Kawabata-Iwakawa; Wataru Kamitani

doi:10.1016/j.virol.2024.110068

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

Virology. 2024 Apr 8:595:110068. doi: 10.1016/j.virol.2024.110068. Online ahead of print.

Authors

Shiori Ueno¹, Sodbayasgalan Amarbayasgalan¹, Yoshiro Sugiura¹, Tatsuki Takahashi¹, Kenta Shimizu¹, Keisuke Nakagawa², Reika Kawabata-Iwakawa³, Wataru Kamitani⁴

Affiliations

¹ Department of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, Gunma, Japan.
² Laboratory of Veterinary Microbiology, Joint Department of Veterinary Medicine, Gifu University, Yanagido, Gifu, Japan.
³ Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Gunma University, Gunma, Japan.
⁴ Department of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, Gunma, Japan. Electronic address: wakamita@gunma-u.ac.jp.

PMID: 38593595
DOI: 10.1016/j.virol.2024.110068

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.