HSV usurps eukaryotic initiation factor 3 subunit M for viral protein translation: Novel prevention target

Natalia V. Cheshenko, Janie B. Trepanier, Theodore J. Segarra, A. Oveta Fuller, Betsy Herold

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Prevention of genital herpes is a global health priority. B5, a recently identified ubiquitous human protein, was proposed as a candidate HSV entry receptor. The current studies explored its role in HSV infection. Viral plaque formation was reduced by ~90% in human cells transfected with small interfering RNA targeting B5 or nectin-1, an established entry receptor. However, the mechanisms were distinct. Silencing of nectin-1 prevented intracellular delivery of viral capsids, nuclear transport of a viral tegument protein, and release of calcium stores required for entry. In contrast, B5 silencing had no effect on these markers of entry, but inhibited viral protein translation. Specifically, viral immediate early genes, ICP0 and ICP4, were transcribed, polyadenylated and transported from the nucleus to the cytoplasm, but the viral transcripts did not associate with ribosomes or polysomes in B5-silenced cells. In contrast, immediate early gene viral transcripts were detected in polysome fractions isolated from control cells. These findings are consistent with sequencing studies demonstrating that B5 is eukaryotic initiation factor 3 subunit m (eIF3m). Although B5 silencing altered the polysome profile of cells, silencing had little effect on cellular RNA or protein expression and was not cytotoxic, suggesting that this subunit is not essential for host cellular protein synthesis. Together these results demonstrate that B5 plays a major role in the initiation of HSV protein translation and could provide a novel target for strategies to prevent primary and recurrent herpetic disease.

Original languageEnglish (US)
Article numbere11829
JournalPLoS One
Volume5
Issue number7
DOIs
StatePublished - 2010

Fingerprint

Eukaryotic Initiation Factor-3
Viral Matrix Proteins
viral proteins
Protein Biosynthesis
translation (genetics)
polyribosomes
Polyribosomes
Immediate-Early Genes
Viral Proteins
Proteins
Translational Peptide Chain Initiation
protein synthesis
cells
Herpes Genitalis
Health Priorities
Genes
receptors
capsid
Cell Nucleus Active Transport
Viral Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

HSV usurps eukaryotic initiation factor 3 subunit M for viral protein translation : Novel prevention target. / Cheshenko, Natalia V.; Trepanier, Janie B.; Segarra, Theodore J.; Fuller, A. Oveta; Herold, Betsy.

In: PLoS One, Vol. 5, No. 7, e11829, 2010.

Research output: Contribution to journalArticle

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