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MicroRNA-based Regulation of Picornavirus Tropism
09:05

MicroRNA-based Regulation of Picornavirus Tropism

Published on: February 6, 2017

Biological effect of Muller's Ratchet: distant capsid site can affect picornavirus protein processing

Cristina Escarmís1, Celia Perales, Esteban Domingo

  • 1Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, C/Nicolás Cabrera 1, 28049 Madrid, Spain.

Journal of Virology
|May 1, 2009
PubMed

Insights

Repeated bottleneck passages in foot-and-mouth disease virus (FMDV) increase thermosensitivity. An M54I substitution in capsid protein VP1 impairs polyprotein processing, leading to viral defects.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • RNA viruses accumulate mutations and lose fitness during repeated bottleneck passages.
  • Foot-and-mouth disease virus (FMDV) is a significant pathogen affecting livestock.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying fitness decrease and increased thermosensitivity in FMDV after bottleneck passages.
  • To identify specific viral lesions responsible for these observed changes.

Main Methods:

  • Construction of infectious FMDV clones.
  • Plaque-to-plaque transfers in BHK-21 cells to simulate bottleneck passages.
  • Analysis of viral protein processing and thermosensitivity.
  • Three-dimensional structural analysis of FMDV particles.

Main Results:

  • Bottleneck passages increased thermosensitivity in FMDV clones.
  • The amino acid substitution M54I in capsid protein VP1 was identified as a key lesion.
  • M54I substitution impaired P1 precursor processing, reducing VP1 production and increasing precursor accumulation, especially at high temperatures.
  • The M54 residue is surface-exposed and near an antigenic site, but not directly at the VP1-VP3 cleavage site.

Conclusions:

  • The M54I substitution in FMDV VP1 causes thermosensitivity by affecting polyprotein processing.
  • This study highlights a distance effect in viral polyprotein processing and the importance of biochemical analysis of viral defects arising from bottleneck events.

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