Temperature-sensitive Poliovirus Mutants Defective in Repression of Host Protein Synthesis are also Defective in Structural Protein

Steiner-Pryor, Amy; Cooper, Penny

doi:10.1099/0022-1317-21-2-215

Cited by 28 publications

(4 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, lysates from poliovirus-infected cells can inactivate eIF-4B when it is added to the lysate (data not shown) or in mixed lysates from infected and uninfected cells. The mechanism of inactivation is not known, but it is presumably carried out by a viral protein (25).…”

Section: Effects Of Initiation Factors In Infected and Uninfectedmentioning

confidence: 99%

Inhibition of translation by poliovirus: inactivation of a specific initiation factor.

Rose¹,

Trachsel²,

Leong³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

182

122

View full text Add to dashboard Cite

Translation of vesicular stomatitis virus (VSV) mRNA, like host mRNA translation, is inhibited in cells infected with poliovirus. To study the mechanism of poliovirus-induced inhibition of protein synthesis, we prepared extracts from poliovirus-infected and uninfected HeLa cells. Poliovirus mRNA was translated in Iysates from both infected and uninfected cells, while VSV mRNA was translated only in the lysate from uninfected cells. Addition of purified translation initiation factors to the extract frosi infected cells showed that one factor eIF4B, could restore VSV mRNA translation in the infected lysate, but did not increase poliovirus mRNA translation. Further experiments involving translation of VSV mRNA in mixed extracts from poliovirus-infected and uninfected cells showed (j) that there was not an excess of an inhibitor of VSV mRNA translation in the infected 1 sate, but (ii) that an activity that caused a slow inactivation oleIF-4B was present in the infected lysate. Inactivation of eIF4B appears to~e the mechanism by which poliovirus -infection causes a selective inhibition of translation. Inhibition of host protein synthesis occurring after virus infection has been demonstrated in many eukaryotic virus-host systems (1). The best studied case of inhibition of protein synthesis is that caused by picornaviruses such as poliovirus, but the mechanism that allows discrimination between host and viral mRNA translation has not been elucidated. Infection by poliovirus results in extensive inhibition of host protein synthesis at the initiation step (2, 3). During poliovirus infection the host mRNAs are not degraded (2, 3) and their capping, methylation, and polyadenylation are not affected (4). Furthermore, translation of vesicular stomatitis virus (VSV) mRNAs is prevented when VSV-infected cells are superinfected with poliovirus (5, 6). VSV mRNA synthesis continues normally in the superinfected cells and the untranslated VSV mRNA can be translated in vitro after purification from the infected cell (6). Also, the kinetics of poliovirus inhibition of host and VSV protein synthesis are identical, suggesting that they occur by the same mechanism (6).In this study we have used translation of VSV mRNA in extracts derived from poliovirus-infected and uninfected HeLa cells to study the mechanism of translation inhibition by poliovirus. VSV directs the synthesis of five mRNAs that encode the five viral proteins (7,8). These mRNAs, like cellular mRNAs, have capped and methylated 5' termini that are important in ribosome recognition (9). In contrast, poliovirus mRNA has a 5' terminus of pUp (10, 11). The evidence presented here indicates that loss of a single initiation factor activity (eIF-4B) can explain the inhibition of VSV and host mRNA translation by poliovirus. Other work has indicated that this factor interacts with the 5' cap structure on mRNA (12). Thus, poliovirus mRNA may bypass the cap-dependent recognitionThe costs of publication of this article were defrayed in part by the payment of page charges. Th...

show abstract

Section: Effects Of Initiation Factors In Infected and Uninfectedmentioning

confidence: 99%

Inhibition of translation by poliovirus: inactivation of a specific initiation factor.

Rose¹,

Trachsel²,

Leong³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

182

122

View full text Add to dashboard Cite

show abstract

“…Alternatively, the picornaviruses appear to require the synthesis of a virus-specified function to arrest the host (1, 6, 25, 36). The possibility that a picornavirus structural component contributes to shutoff has not been completely dismissed (12,27,33). Infection with HSV results in the rapid shutoff of host protein synthesis and is accompanied by dissociation of the polyribosomes (13,34,35).…”

Section: Figmentioning

confidence: 99%

Requirement of protein synthesis for the degradation of host mRNA in Friend erythroleukemia cells infected wtih herpes simplex virus type 1

Nishioka¹,

Silverstein²

1978

J Virol

108

View full text Add to dashboard Cite

We describe experiments which demonstrate that shortly after infection of Friend erythroleukemia cells with herpes simplex virus (HSV), polyribosomes dissociate and cellular mRNA degrades. Analysis of infected cell extracts on sucrose density gradients demonstrates that the majority of the polyribosomes have dissociated to monoribosomes at 2 h postinfection. Physical measurements of infected-cell RNAs support this conclusion and demonstrate that the polyadenylated RNAs decrease in size. The degradation of mRNA is apparently a stochastic process as judged by the failure to detect a shift in the Crtl/2 when

show abstract

“…Also, infection in the presence of 1 mM guanidine, which prevents detectable viral replication and translation, does not seem to affect host cell shutoff at higher multiplicities of infection (MOIs) (7,16). Using temperature-sensitive mutants to examine this problem, Steiner-Pryor and Cooper (20) showed that the ability to inhibit host cell protein synthesis seems to map in the region of the structural protein genes. However, Cole and Baltimore demonstrated that defective interfering polio virions are able to inhibit host cell translation despite the fact that their defectiveness originated because of deletions in the capsid genes and resulted in an inability to specify for structural proteins (3).…”

mentioning

confidence: 99%

Inhibition of host cell protein synthesis by UV-inactivated poliovirus

Helentjaris¹,

Ehrenfeld²

1977

J Virol

View full text Add to dashboard Cite

The ability of poliovirus that was irradiated with UV light at energies up to 2,160 ergs/mm2 to subsequently inhibit host cell protein synthesis was measured. The inactivation ofthe host cell shutoff function followed one-hit kinetics. Increasing irradiation did not affect the rate of inhibition until the multiplicity of infection after irradiation was reduced to approximately 1 PFU/cell. At higher functional multiplicities, the rate was unchanged, but an increasing lag before the onset of inhibition was observed with increasing irradiation. The energy levels required to inactivate virus-induced inhibition of host cell protein synthesis suggest that damage to virus RNA rather than to virus capsid proteins is responsible for the loss offunction. When the inactivation ofhost cell shutoffwas compared with the inactivation of other viral functions by UV irradiation, it correlated exactly with the loss of infectivity but not with other viral functions measured. Guanidine treatment, which prevents detectable viral RNA and protein synthesis, completely inhibited host cell shutoff by low multiplicities of unirradiated virus infection but not higher multiplicities. When a high multiplicity of virus was first reduced to a low titer by irradiation, host cell shutoff was still evident in the presence of guanidine. The results demonstrate that the complete inhibition of host cell protein synthesis can be accomplished by one infectious viral genome per cell.

show abstract

Temperature-sensitive Poliovirus Mutants Defective in Repression of Host Protein Synthesis are also Defective in Structural Protein

Cited by 28 publications

References 18 publications

Inhibition of translation by poliovirus: inactivation of a specific initiation factor.

Inhibition of translation by poliovirus: inactivation of a specific initiation factor.

Requirement of protein synthesis for the degradation of host mRNA in Friend erythroleukemia cells infected wtih herpes simplex virus type 1

Inhibition of host cell protein synthesis by UV-inactivated poliovirus

Contact Info

Product

Resources

About