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

Ting Wei; Dongsheng Li; Daneth Marcial; Moshin Khan; Min-Hsuan Lin; Natale Snape; Reena Ghildyal; David Harrich; Kirsten Spann

doi:10.1371/journal.pone.0114447

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.

Authors

Ting Wei¹, Dongsheng Li¹, Daneth Marcial², Moshin Khan³, Min-Hsuan Lin¹, Natale Snape⁴, Reena Ghildyal⁵, David Harrich⁶, Kirsten Spann⁷

Affiliations

¹ Queensland Institute of Medical Research Berghofer, Herston, Australia.
² Queensland Institute of Medical Research Berghofer, Herston, Australia; Clinical Medical Virology Centre, The University of Queensland, Herston, Australia; Sir Albert Sakzewski Virus Research Centre, Childrens Health Queensland, Herston, Australia.
³ Queensland Institute of Medical Research Berghofer, Herston, Australia; Sir Albert Sakzewski Virus Research Centre, Childrens Health Queensland, Herston, Australia.
⁴ Clinical Medical Virology Centre, The University of Queensland, Herston, Australia; Sir Albert Sakzewski Virus Research Centre, Childrens Health Queensland, Herston, Australia.
⁵ Centre for Research in Therapeutic Solutions, University of Canberra, Canberra, Australia.
⁶ Queensland Institute of Medical Research Berghofer, Herston, Australia; Australian Infectious Disease Research Centre, St Lucia, Australia.
⁷ Clinical Medical Virology Centre, The University of Queensland, Herston, Australia; Sir Albert Sakzewski Virus Research Centre, Childrens Health Queensland, Herston, Australia; Australian Infectious Disease Research Centre, St Lucia, Australia.

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

Grants and funding

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.