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PMID: 3023655 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cellular mRNA translation is blocked at both initiation and elongation after infection by influenza virus or adenovirus.

Journal of virology ·Vol. 60 ·No. 3 ·1986-12-00 ·Pages 1027-39

Katze MG, DeCorato D, Krug RM

Abstract

During influenza virus infection, protein synthesis is maintained at high levels and a dramatic switch from cellular to viral protein synthesis occurs despite the presence of high levels of functional cellular mRNAs in the cytoplasm of infected cells (M. G. Katze and R. M. Krug, Mol. Cell. Biol. 4:2198-2206, 1984). To determine the step at which the block in cellular mRNA translation occurs, we compared the polysome association of several representative cellular mRNAs (actin, glyceraldehyde-3-phosphate dehydrogenase, and pHe7 mRNAs) in infected and uninfected HeLa cells. We showed that most of these cellular mRNAs remained polysome associated after influenza viral infection, indicating that the elongation of the proteins encoded by these cellular mRNAs was severely inhibited. Because the polysomes containing these cellular mRNAs did not increase in size but either remained the same size or decreased in size, the initiation step in cellular protein synthesis must also have been defective. Several control experiments established that the cellular mRNAs sedimenting in the polysome region of sucrose gradients were in fact associated with polyribosomes. Most definitively, puromycin treatment of infected cells caused the dissociation of polysomes and the release of cellular, as well as viral, mRNAs from the polysomes, indicating that the cellular mRNAs were associated with polysomes that were capable of forming at least a single peptide bond. A similar analysis was performed with HeLa cells infected by adenovirus, which also dramatically shuts down cellular protein synthesis. Again, it was found that most of the cellular mRNAs, which were translatable in reticulocyte extracts, remained associated with polysomes and that there was a combined initiation-elongation block to cellular protein synthesis. In cells infected by both adenovirus and influenza virus, influenza viral mRNAs were on larger polysomes than were several late adenoviral mRNAs with comparably sized coding regions. In addition, after influenza virus superinfection of cells infected by the adenovirus mutant dl331, a situation in which there is a limitation in the amount of functional initiation factor eIF-2 (M. G. Katze, B. M. Detjen, B. Safer, and R. M. Krug, Mol. Cell. Biol. 6:1741-1750, 1986), influenza viral mRNAs, but not late adenoviral mRNAs, were on polysomes. These results indicate that influenza viral mRNAs are better initiators of translation than are late adenoviral mRNAs.

MeSH Terms
Adenoviridae Infections/genetics Adenoviruses, Human/genetics Gene Expression Regulation HeLa Cells Humans Influenza A virus/genetics Influenza, Human/genetics Peptide Chain Elongation, Translational Peptide Chain Initiation, Translational Polyribosomes/metabolism RNA, Messenger/metabolism RNA, Viral/genetics
Chemicals
RNA, Messenger RNA, Viral
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Katze M G
DeCorato D
Krug R M
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59 references, click to expand
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.60.3.1027-1039.1986
Published
1986-12-00
Pages
1027-39
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC253342
Subset
IM
Grants
NIAID NIH HHS · AI 117722 · United States
NCI NIH HHS · CA 08747 · United States
External Links
PubMed source DOI: 10.1128/JVI.60.3.1027-1039.1986 PMC Full Text View journal details
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