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MERS coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral RNA

Yutaka Terada1, Kengo Kawachi2, Yoshiharu Matsuura3

  • 1Laboratory of Clinical Research on Infectious Diseases, Osaka University, Osaka 565-0871, Japan.

Virology
|August 27, 2017
PubMed

Insights

Middle East Respiratory Syndrome-associated Coronavirus (MERS-CoV) non-structural protein 1 (nsp1) is a virulence factor. This study identifies key MERS-CoV nsp1 residues and a cis-acting element crucial for viral replication by overcoming host protein synthesis shutoff.

Area of Science:

  • Virology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Middle East Respiratory Syndrome-associated Coronavirus (MERS-CoV) is a lethal human coronavirus endemic in the Arabian Peninsula.
  • No vaccines or therapeutics are currently available for MERS-CoV infection.
  • The MERS-CoV non-structural protein 1 (nsp1) is a key virulence factor, suppressing host protein synthesis via mRNA degradation.

Purpose of the Study:

  • To identify critical amino acid residues in MERS-CoV nsp1 responsible for circumventing host translational shutoff.
  • To investigate the role of cis-acting elements in MERS-CoV RNA in viral replication.

Main Methods:

  • Comparative analysis of MERS-CoV and SARS-CoV nsp1 sequences to identify differing residues.
  • Reverse genetics analysis to study the function of the 5'-terminus of the nsp1-coding region.

Main Results:

  • Specific amino acid residues in MERS-CoV nsp1 were identified as crucial for overcoming the nsp1-mediated translational shutoff.
  • A cis-acting element at the 5'-terminus of the nsp1-coding region was found to be essential for viral RNA recognition and efficient replication.

Conclusions:

  • MERS-CoV nsp1 possesses unique features that enable it to evade host defenses.
  • A common mechanism for coronaviruses to circumvent nsp1-mediated translational shutoff likely exists, involving both viral protein and RNA elements.
Keywords:
CoronavirusMERS-CoVNsp1RNA recognitionViral replication

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