Functional advantages of triplication of the 3B coding region of the FMDV genome

Oluwapelumi O Adeyemi1,2, Joseph C Ward1, Joseph S Snowden1

  • 1School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.

Insights

Foot-and-mouth disease virus (FMDV) uniquely uses multiple copies of the VPg (3B) protein for replication. More copies enhance viral replication, with distinct cis and trans functions evolving for multiple 3B proteins.

Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Gene duplication in RNA viruses is rare and suggests functional advantages.
  • Foot-and-mouth disease virus (FMDV) is unique among picornaviruses for possessing three copies of the VPg (3B) protein-coding region.
  • The VPg (3B) protein functions as a primer for viral RNA replication.

Purpose of the Study:

  • To investigate the functional contributions and structural requirements of individual VPg (3B) protein copies in FMDV replication.
  • To understand the selective pressures maintaining multiple VPg (3B) copies in the FMDV genome.

Main Methods:

  • Utilized sub-genomic replicons with nonfunctional 3B proteins and 3B fusion products.
  • Employed competition and complementation assays to assess VPg (3B) functionality.
  • Investigated requirements for both cis and trans replication.

Main Results:

  • A free N-terminus is essential for VPg (3B) to act as a primer.
  • While one VPg (3B) copy supports genome replication, additional copies confer a competitive advantage, up to a point.
  • A minimum of two VPg (3B) copies are required for trans replication, unlike other picornaviruses.

Conclusions:

  • VPg (3B) copy number expansion in FMDV likely facilitated the evolution of separate cis and trans replication functions.
  • This functional specialization provides a selective advantage for maintaining multiple VPg (3B) copies in the FMDV genome.

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