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Related Experiment Video

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Assays for the Specific Growth Rate and Cell-binding Ability of Rotavirus
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Nucleolin-RNA interaction modulates rotavirus replication.

Jey Hernández-Guzmán1, Carlos F Arias1, Susana López1

  • 1Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.

Journal of Virology
|January 19, 2024
PubMed
Summary
This summary is machine-generated.

Nucleolin protein negatively regulates rotavirus replication by binding to viral RNA G-quadruplex structures. Inhibiting this interaction boosts infectious rotavirus production, revealing a new regulatory mechanism in viral cycles.

Keywords:
RNA-binding proteinnucleolinrotavirusvirus–host cell interactions

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Generation and Assembly of Virus-Specific Nucleocapsids of the Respiratory Syncytial Virus
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Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Rotavirus is a major cause of childhood gastroenteritis globally, with a dsRNA genome within a protein capsid.
  • Cellular proteins involved in rotavirus replication, particularly RNA-binding proteins, are not well understood.
  • Nucleolin is a multifunctional RNA-binding protein involved in various cellular processes.

Purpose of the Study:

  • To investigate the role of nucleolin in rotavirus infection and replication.
  • To elucidate the mechanism by which nucleolin affects rotavirus production.
  • To identify potential therapeutic targets for rotavirus by understanding host-pathogen interactions.

Main Methods:

  • RNA interference was used to knock down nucleolin expression in MA104 cells.
  • MA104 cells were transfected with AGRO100, a G4 structure-forming compound, to inhibit nucleolin-RNA interactions.
  • G-quadruplex (G4) sequences in rotavirus RNA were identified and their role assessed via oligonucleotide transfection.

Main Results:

  • Nucleolin knockdown significantly increased infectious rhesus rotavirus (RRV) progeny production (6.3-fold), viral mRNA, and genome copies.
  • Inhibition of nucleolin-RNA interaction with AGRO100 resulted in a 1.5-fold increase in viral production.
  • G4 sequences were found in all 11 RRV dsRNA segments, and their mimicry increased viral production.

Conclusions:

  • Nucleolin negatively regulates rotavirus replication through direct interaction with viral RNA via G-quadruplex structures.
  • This interaction inhibits the yield of infectious viral particles, suggesting nucleolin acts as a host restriction factor.
  • The findings introduce a novel regulatory mechanism in rotavirus replication involving host RNA-binding proteins and viral RNA G4 structures.