The eukaryotic elongation factor 1A is critical for genome replication of the paramyxovirus respiratory syncytial virus

PLoS One. 2014 Dec 5;9(12):e114447. doi: 10.1371/journal.pone.0114447. eCollection 2014.

Abstract

The eukaryotic translation factor eEF1A assists replication of many RNA viruses by various mechanisms. Here we show that down-regulation of eEF1A restricts the expression of viral genomic RNA and the release of infectious virus, demonstrating a biological requirement for eEF1A in the respiratory syncytial virus (RSV) life cycle. The key proteins in the replicase/transcriptase complex of RSV; the nucleocapsid (N) protein, phosphoprotein (P) and matrix (M) protein, all associate with eEF1A in RSV infected cells, although N is the strongest binding partner. Using individually expressed proteins, N, but not P or M bound to eEF1A. This study demonstrates a novel interaction between eEF1A and the RSV replication complex, through binding to N protein, to facilitate genomic RNA synthesis and virus production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Viral / physiology
  • Genome, Viral / physiology*
  • HEK293 Cells
  • Humans
  • Peptide Elongation Factor 1 / metabolism*
  • Respiratory Syncytial Virus Infections / metabolism*
  • Respiratory Syncytial Viruses / physiology*
  • Viral Proteins / biosynthesis
  • Virus Replication / physiology*

Substances

  • Peptide Elongation Factor 1
  • Viral Proteins

Grant support

This study was funded by the Australian National Health and Medical Research Council Project Grant #1065121 to DH and KS (https://www.nhmrc.gov.au/); Australian Infectious Diseases Research Centre project grant to KS and DH (www.aidrc.org.au/); Australian National Health and Medical Research Council Biomedical Early Career Development Fellowship to TW; and Australian Research Council Future Fellowship to DH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.