Translational control by adenovirus: Lack of virus-associated RNA(I) during adenovirus infection results in phosphorylation of initiation factor eIF-2 and inhibition of protein synthesis

J. Siekierka, T. M. Mariano, P. A. Reichel, M. B. Mathews

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

The dl331 mutant of adenovirus serotype 5 fails to produce virus-associated (VA) RNA(I), and cells infected with this mutant do not synthesize proteins efficiently at late times in infection. The translational defect occurs at the level of polypeptide chain initiation, and cell-free extracts prepared from dl331-infected cells exhibit the defect observed in vivo. Addition of either eukaryotic initiation factor 2 (eIF-2) or guanine nucleotide exchange factor (GEF) to these cell-free extracts restores translational activity, with GEF functioning more efficiently in this regard. These results suggest that cells infected with the dl331 mutant develop a translational block at the level of GEF-catalyzed guanine nucleotide exchange and that this block is most likely established through phosphorylation of the α subunit of eIF-2. In the present investigation we show that endogenous HeLa cell GEF activity is significantly reduced in cells infected with the dl331 mutant. Further, in contrast to cells infected with wild-type serotype 2 adenovirus, dl331-infected cells contain increased eIF-2α kinase activity. These results indicate that VA RNA(I) plays a role in suppressing eIF-2α kinase activity during adenovirus infection of HeLa cells.

Original languageEnglish
Pages (from-to)1959-1963
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume82
Issue number7
DOIs
StatePublished - 1 Jan 1985

Fingerprint Dive into the research topics of 'Translational control by adenovirus: Lack of virus-associated RNA(I) during adenovirus infection results in phosphorylation of initiation factor eIF-2 and inhibition of protein synthesis'. Together they form a unique fingerprint.

  • Cite this