Inhibition of cell functions by RNA-virus infections

Annu Rev Microbiol. 1984:38:91-109. doi: 10.1146/annurev.mi.38.100184.000515.

Abstract

The studies with poliovirus have revealed that cells have a full capacity to translate uncapped mRNA, although their own mRNAs are capped and methylated. These observations have been confirmed by translation studies in fractionated systems in vitro. In poliovirus-infected cells, and in cell extracts prepared from them, a well-documented loss of capacity to translate capped mRNAs has been shown. This is due to the dissociation of cap-binding protein(s) from the initiation factor eIF-3. It has not been possible to show which virus-specific protein, if any, is responsible for this dissociation. It may be that once not used, the cap-binding protein is excluded passively from its normal association cycle with eIF-3, rendering the cells incapable of translating capped mRNAs. Late in reovirus infection a similar phenomenon is observed. The secondary transcription products of reovirus subviral particles are uncapped mRNAs, which are synthesized in abundance. Their capping and methylation is prevented in the SVPs due to a masking of the respective enzymes. The inability to translate capped mRNAs in lysates prepared from reovirus-infected cells, late in infection, may be due to a similar mechanism, as in poliovirus-infected cells. Simply, a large excess of uncapped mRNA competes with initiation factors without specific need for the cap-binding protein(s), which becomes dissociated from the eIF-3 and loses its activity. Inhibition of host protein synthesis, whether due to simple competition or specified by a viral gene product, leads apparently to a shortage of initiation factors and ribosomes, causing the cessation of translation of both capped and uncapped mRNA, and finally to cell death. The studies with UV-inactivated VSV, its temperature-sensitive mutants and defective-interfering LT-particles clearly suggest that inhibition of host-cell macromolecular synthesis can be induced by mechanisms that do not operate during normal VSV-infection. It may be that similar phenomena occur in guanidine-treated poliovirus-infected cells. In these cells the host protein synthesis is inhibited as a result of the translation of a few hundred incoming viral RNAs. It would be interesting to know whether the cap-binding protein is dissociated from initiation factors under these conditions. If not, another mechanism has to be revealed, which again may not be manifest during normal poliovirus infection. The inhibition of host RNA and DNA synthesized by various viruses has been less intensively studied than inhibition of protein synthesis. Apparently, good in vitro systems are needed to solve these difficult problems.

Publication types

  • Review

MeSH terms

  • Alphavirus / genetics
  • Animals
  • Carrier Proteins / genetics
  • Cell Transformation, Viral*
  • DNA Replication
  • HeLa Cells / metabolism
  • Humans
  • Peptide Initiation Factors / genetics
  • Picornaviridae / genetics
  • Protein Biosynthesis
  • RNA Cap-Binding Proteins
  • RNA Viruses / genetics*
  • RNA, Messenger / genetics
  • Transcription, Genetic
  • Vesicular stomatitis Indiana virus / genetics

Substances

  • Carrier Proteins
  • Peptide Initiation Factors
  • RNA Cap-Binding Proteins
  • RNA, Messenger