Recombinant respiratory syncytial virus F protein expression is hindered by inefficient nuclear export and mRNA processing

Virus Genes. 2010 Apr;40(2):212-21. doi: 10.1007/s11262-010-0449-8. Epub 2010 Jan 29.

Abstract

Studies of the fusion activity of respiratory syncytial virus (RSV) F protein are significantly hindered by low recombinant expression levels. While infection produces F protein levels detectable by western blot, recombinant expression produces undetectable to low levels of F protein. Identifying the obstacles that hinder recombinant F protein expression may lead to improved expression and facilitate the study of F protein function. We hypothesized that nuclear localization and/or inefficient RNA polymerase II-mediated transcription contribute to poor recombinant F protein expression. This study shows a combination of stalled nuclear export, premature polyadenylation, and low mRNA abundance all contribute to low recombinant F protein expression levels. In addition, this study provides an expression optimization strategy that results in greater F protein expression levels than observed by codon-optimization of the F protein gene, which will be useful for future studies of F protein function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus*
  • Animals
  • Cell Line
  • Gene Expression*
  • Humans
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / metabolism*
  • RNA, Viral / metabolism*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Viral Fusion Proteins / biosynthesis*
  • Viral Fusion Proteins / genetics

Substances

  • F protein, human respiratory syncytial virus
  • RNA, Messenger
  • RNA, Viral
  • Recombinant Proteins
  • Viral Fusion Proteins