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SARS-CoV-2-encoded inhibitors of human LINE-1 retrotransposition

Yan Li1, Jiaxin Yang1, Siyu Shen1

  • 1Institute of Virology and AIDS Research, First Hospital, Jilin University, Changchun, Jilin, China.

Journal of Medical Virology
|September 10, 2022
PubMed

Insights

Severe acute respiratory coronavirus 2 (SARS-CoV-2) viral proteins suppress the activity of human long interspersed element 1 (L1) retrotransposons. This study reveals SARS-CoV-2 modulates host genetic elements to optimize its intracellular environment.

Area of Science:

  • Molecular Biology
  • Virology
  • Genetics

Background:

  • Severe acute respiratory coronavirus 2 (SARS-CoV-2) significantly impacts global public health.
  • The precise mechanisms by which SARS-CoV-2 affects host cells are not fully understood.
  • Long interspersed element 1 (L1) retrotransposons are mobile genetic elements with implications in genome stability and immune responses.

Purpose of the Study:

  • To investigate the impact of SARS-CoV-2-encoded viral proteins on the intracellular activity of human L1 retrotransposons.
  • To identify specific SARS-CoV-2 proteins that modulate L1 retrotransposon mobility.
  • To elucidate the mechanisms by which SARS-CoV-2 proteins inhibit L1 transposition.

Main Methods:

  • Utilized established reporter systems to assess L1 retrotransposon activity.
  • Examined the effects of several SARS-CoV-2 nonstructural proteins (Nsps) including Nsp1, Nsp3, Nsp5, and Nsp14.
  • Analyzed the impact of viral proteins on L1 open reading frame proteins (ORF1p) accumulation and L1 ORF2p reverse transcriptase activity.

Main Results:

  • Several SARS-CoV-2 Nsps (Nsp1, Nsp3, Nsp5, and Nsp14) were found to significantly suppress human L1 mobility.
  • Nsp1 and Nsp14 were identified as inhibitors of intracellular L1 ORF1p accumulation.
  • Nsp3, Nsp5, and Nsp14 were shown to repress the reverse transcriptase activity of L1 ORF2p.

Conclusions:

  • SARS-CoV-2 employs viral proteins to inhibit L1 retrotransposon activity, forming a complex regulatory network.
  • These anti-L1 activities suggest SARS-CoV-2 manipulates the host genetic environment to its advantage.
  • Understanding these interactions provides insights into viral pathogenesis and host-virus dynamics.
Keywords:
LINE-1SARS-CoV-2coronavirusretrotransposon

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