Untranslated vesicular stomatitis virus messenger RNA after poliovirus infection

doi:10.1016/S0042-6822(77)80006-8

Virology

Volume 80, Issue 2, 15 July 1977, Pages 297-308

https://doi.org/10.1016/S0042-6822(77)80006-8 Get rights and content

Superinfection of vesicular stomatitis virus (VSV)-infected cells with poliovirus causes a complete inhibition of VSV-directed protein synthesis, followed by normal replication of poliovirus. The “shut-off” of VSV protein synthesis appears similar in all respects to the inhibition of host cell protein synthesis normally induced by poliovirus infection. VSV messenger RNA (mRNA) synthesis continues at normal rates after superinfection. This RNA appears to accumulate and to remain intact, although it does not associate with ribosomes. The untranslated RNA is polyadenylated, capped, and methylated normally. Furthermore, when extracted from superinfected cells, it manifests normal biological function, measured by its ability to stimulate the synthesis of VSV proteins by a cell-free wheat germ protein-synthesizing extract. Thus, the inhibition of protein synthesis by poliovirus does not seem to be the result of a modification or inactivation of messenger RNA.

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A hypothesis on the mechanism of translational initiation
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Expression of poliovirus 2A<sup>pro</sup> in mammalian cells: effects on translation
1995, FEBS Letters
Poliovirus protease 2A^pro has been efficiently expressed in HeLa and COS cells upon transfection with vector pTM1-2A and infection with the recombinant vaccinia virus bearing the T7 RNA polymerase. The expressed poliovirus protease localizes to the cytoplasm of the transfected cells, both in the endoplasmic reticulum and in vesicles scattered in the cytoplasm. Cleavage of p220, a component of initiation factor eIF-4F, selectively occurs from 5 h post-infection in transfected cells infected with the recombinant virus. This cleavage correlates in time with the profound inhibition observed in the synthesis of vaccinia virus proteins. A similar blockade of vesicular stomatitis virus translation takes place upon 2A^pro expression. Finally, the synthesis of poliovirus protein 2C from a recombinant vaccinia virus that expresses this protein under the EMC untranslated leader region is not affected by the synthesis of 2A^pro. These findings lend support to the idea that translation of capped mRNAs requires the integrity of p220, while this requirement is not observed when translation of a mRNA bearing a picornavirus leader region is assayed.
Inhibition of host cell protein synthesis in poliovirus-infected cells
1993, Seminars in Virology
Poliovirus infection of HeLa cells in culture causes rapid inhibition of host cell protein synthesis, while viral proteins are synthesized at high levels. This inhibition correlates with the inactivation of eukaryotic initiation factor 4F (eIF-4F), by proteolytic cleavage of its γ-subunit, p220. eIF-4F is required for the translation of capped mRNAs. Poliovirus RNA is uncapped and is translated by a cap independent mechanism. The poliovirus protease, 2A^pro, is required for p220 cleavage, but induces this cleavage indirectly by activating a host protease that catalyzes p220 cleavage. Eukaryotic initiation factor 3 is also required for p220 cleavage, but its role in the cleavage reaction is unknown.
Regulation of translation by poliovirus
1987, Advances in Virus Research
This chapter discusses the regulation of translation by poliovirus. It emphasizes recent developments—especially with regard to the function of cap binding proteins—in translation initiation and their modification following poliovirus infection. There is currently a general agreement about the mechanism by which poliovirus infection effects cessation of host protein synthesis. Consequently, the chapter emphasizes the work that led to the model for shutoff, which best fits the available data—that is, a cap binding protein function that is an essential activity for translation of cellular mRNAs, but somehow not required for poliovirus translation, is inactivated following poliovirus infection. The discussion also deals with possible viral mediators of the shutoff phenomenon. Several alternative models proposed to explain the shutoff phenomenon are evaluated with respect to their likelihood of being applicable to poliovirus infection.
The effect of poliovirus infection on the translation In Vitro of VSV messenger ribonucleoprotein particles
1983, Virology
Messenger ribonucleoprotein (mRNP) particles were isolated and examined for the presence of factors involved in the inhibition of protein synthesis induced by poliovirus infection. Vesicular stomatitis virus (VSV) mRNNs were used as a model for cellular mRNNs. These mRNNs were translated in HeLa cell extracts with a similar efficiency and optimal conditions to that of purified mRNA, but they were not translated in extracts prepared from poliovirus-infected HeLa cells, which have been shown to be defective in cap-binding protein activity. We conclude that mRNP proteins do not include cap-binding protein activity, since the mRNNs were not able to bypass the restriction on translation of capped mRNAs in polio-infected cell extracts. In addition, VSV mRNNs were isolated from polio-superinfected cells, in which their translation was inhibited. These mRNNs were translated in vitro as well as normal VSV mRNNs. No evidence of a modification or a blocking factor on the mRNNs which prevented their translation following polio infection was observed. Thus, within the limits of the in vitro translation assays used, no factors involved in the discrimination between polioviral and cellular or VSV mRNA could be detected in the mRNP particle.
Regulation of protein synthesis in HEp-2 cells and their cytoplasmic extracts after poliovirus infection
1981, Virology
In intact HEp-2 cells, the overall rate of protein synthesis decreased rapidly after poliovirus infection. Under the controlled energetic and ionic in vitro assay conditions, however, cytoplasmic extracts prepared late in infection exhibited an increased translational activity. This resulted from multiple reinitiation cycles of poliovirus RNA translation. Increased ion concentrations in the in vitro translation reaction mixtures inhibited both the rate of peptide chain initiation and elongation for cellular mRNA translation. However, excess salts inhibited the rate of polypeptide chain elongation for poliovirus in vitro translation to a higher extent than the rate of initiation. A virus-induced shut off of host cell protein synthesis was observed in vivo as well as in the in vitro translation system. Translation of cellular mRNAs in cytoplasmic extracts prepared late in infection was restored by addition of uninfected cell extract free of endogenous mRNA. We concluded that increased concentrations of ions in poliovirus-infected cells account for the decrease in the overall rate of protein synthesis, but are not involved in the mechanism of poliovirus-induced shut off of host cell protein synthesis.

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Virology

References (26)

Studies on the in vitro transcription and translation of vesicular stomatitis virus mRNA

Virology

Replication of SV5 RNA and the effects of superinfection with poliovirus

Virology

An improved agar cell-suspension plaque assay for poliovirus: Some factors affecting efficiency of plating

Virology

Studies of the inhibitory action of guanidine on poliovirus multiplication in cell cultures

Virology

Mycoplasma contamination of animal cell cultures: A simple, rapid detection method

Exp. Cell Res.

Methylated and blocked 5′ termini in vesicular stomatitis virus in vivo mRNAs

Cell

Studies on the in vivo messenger RNA species of vesicular stomatitis virus

Virology

Protein synthesis in vesicular stomatitis virus-infected HeLa cells

Virology

Heterogeneous 5′ terminal structures occur on vesicular stomatitis virus mRNAs

J. Biol. Chem.

Restriction of herpes simplex virus replication by poliovirus: A selective inhibition of viral translation

Virology

The mechanism of host cell protein synthesis inhibition by poliovirus

Virology

Translation and identification of the viral mRNA species isolated from subcellular fractions of vesicular stomatitis virus-infected cells

J. Virol

Fate of messenger RNA of L cells infected with mengovirus

J. Virol.

Cited by (23)

A hypothesis on the mechanism of translational initiation

Expression of poliovirus 2A<sup>pro</sup> in mammalian cells: effects on translation

Inhibition of host cell protein synthesis in poliovirus-infected cells

Regulation of translation by poliovirus

The effect of poliovirus infection on the translation In Vitro of VSV messenger ribonucleoprotein particles

Regulation of protein synthesis in HEp-2 cells and their cytoplasmic extracts after poliovirus infection