Herpes simplex virus proteins ICP27 and UL47 associate with polyadenylate-binding protein and control its subcellular distribution

J Virol. 2010 Jan;84(1):270-9. doi: 10.1128/JVI.01740-09.

Abstract

Human pathogenic viruses manipulate host cell translation machinery to ensure efficient expression of viral genes and to thwart host cell protein synthesis. Viral strategies include cleaving translation factors, manipulating translation factor abundance and recruitment into translation initiation complexes, or expressing viral translation factor analogs. Analyzing translation factors in herpes simplex virus type 1 (HSV-1)-infected HeLa cells, we found diminished association of the polyadenylate-binding protein (PABP) with the cap-binding complex. Although total PABP levels were unchanged, HSV-1 infection prompted accumulation of cytoplasmic PABPC1, but not its physiologic binding partner PABP-interacting protein 2 (Paip2), in the nucleus. Using glutathione S-transferase-PABP pull-down and proteomic analyses, we identified several viral proteins interacting with PABPC1 including tegument protein UL47 and infected-cell protein ICP27. Transient expression of ICP27 and UL47 in HeLa cells suggested that ICP27 and UL47 jointly displace Paip2 from PABP. ICP27 expression alone was sufficient to cause PABPC1 redistribution to the nucleus. ICP27 and UL47 did not alter translation efficiency of transfected reporter RNAs but modulated transcript abundance and expression of reporter cDNAs in transfected cells. This indicates that redistribution of PABPC1 may be involved in co- and posttranscriptional regulation of mRNA processing and/or nuclear export by HSV-1 gene regulatory proteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Gene Expression Regulation
  • HeLa Cells
  • Herpes Simplex
  • Herpesvirus 1, Human / physiology*
  • Humans
  • Immediate-Early Proteins / metabolism*
  • Peptide Initiation Factors / metabolism
  • Poly(A)-Binding Protein I / metabolism*
  • Protein Binding
  • RNA, Messenger / analysis
  • RNA-Binding Proteins / metabolism
  • Repressor Proteins / metabolism
  • Viral Fusion Proteins / metabolism*

Substances

  • ICP27 protein, human herpesvirus 1
  • Immediate-Early Proteins
  • PAIP1 protein, human
  • PAIP2 protein, human
  • Peptide Initiation Factors
  • Poly(A)-Binding Protein I
  • RNA, Messenger
  • RNA-Binding Proteins
  • Repressor Proteins
  • VP13-14 protein, herpes simplex virus type 1
  • Viral Fusion Proteins