Initiation activity of EMC virus RNA, binding to initiation factor eIF-4B and shut-off of host cell protein synthesis

Nature ◽  
1978 ◽  
Vol 275 (5677) ◽  
pp. 240-243 ◽  
Author(s):  
CORRADO BAGLIONI ◽  
MARCELLA SIMILI ◽  
DAVID A. SHAFRITZ
Keyword(s):  
Protein Synthesis ◽  
Host Cell ◽  
Rna Binding ◽  
Initiation Factor ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Virus Rna ◽  
Emc Virus

scholarly journals Eukaryotic Initiation Factor 4GII (eIF4GII), but Not eIF4GI, Cleavage Correlates with Inhibition of Host Cell Protein Synthesis after Human Rhinovirus Infection

1999 ◽  
Vol 73 (4) ◽  
pp. 3467-3472 ◽  
Author(s):  
Yuri V. Svitkin ◽  
Alessandra Gradi ◽  
Hiroaki Imataka ◽  
Shigenobu Morino ◽  
Nahum Sonenberg
Keyword(s):  
Protein Synthesis ◽  
Host Cell ◽  
Human Rhinovirus ◽  
Host Protein ◽  
Initiation Factor ◽  
Cell Protein ◽  
Eukaryotic Initiation Factor ◽  
Host Cell Protein ◽  
Rhinovirus Infection ◽  
Host Protein Synthesis

ABSTRACT For many members of the Picornaviridae family, infection of cells results in a shutoff of host protein synthesis. For rhinoviruses and enteroviruses, the shutoff has been explained in part by the cleavage of eukaryotic initiation factor 4GI (eIF4GI), a component of the cap-binding protein complex eIF4F. The cleavage of eIF4GI is mediated by the virus-specific proteinase 2Aproand results in inhibition of cap-dependent, but not cap-independent, translation. The inhibition of host protein synthesis after infection with human rhinovirus 14 (HRV-14) lags behind the cleavage of eIF4GI. Recently, we discovered a functional homolog of eIF4GI, termed eIF4GII, and showed that cleavage of eIF4GII coincides with the shutoff of host cell protein synthesis after poliovirus infection (Gradi et al., Proc. Natl. Acad. Sci. USA 95:11089–11094, 1998). We wished to determine whether eIF4GII cleavage kinetics could also explain the lack of correlation between the kinetics of eIF4GI cleavage and the shutoff of host protein synthesis after rhinovirus infection. In this study, we examined the correlation between human rhinovirus-induced shutoff of host protein synthesis and cleavage of eIF4GI and eIF4GII. In HRV-14-infected HeLa cells, almost no intact eIF4GI could be detected by 4 h postinfection, while only 4% of eIF4GII was cleaved at this time. By 6 h, however, 67% of eIF4GII was cleaved, and this cleavage coincided with a significant (60%) decline of host translation. These results suggest that cleavage of both eIF4GI and eIF4GII is required for HRV-mediated inhibition of host cell protein synthesis and that the cleavage of eIF4GII is the rate-limiting step in the shutoff of host cell protein synthesis after rhinovirus infection.

scholarly journals Cleavage of eukaryotic initiation factor eIF4G and inhibition of host-cell protein synthesis during feline calicivirus infection

2004 ◽  
Vol 85 (5) ◽  
pp. 1125-1130 ◽  
Author(s):  
Margaret M. Willcocks ◽  
Michael J. Carter ◽  
Lisa O. Roberts
Keyword(s):  
Protein Synthesis ◽  
Host Cell ◽  
Cellular Protein ◽  
Initiation Factor ◽  
Cell Protein ◽  
Feline Calicivirus ◽  
Host Cell Protein ◽  
Eukaryotic Translation ◽  
Initiation Factors ◽  
Eukaryotic Translation Initiation Factors

Caliciviruses are small, non-enveloped, positive-stranded RNA viruses that are pathogenic for both animals and man. Although their capsid structure and genomic organization are distinct from picornaviruses, they have similarities to these viruses in their non-structural proteins. Picornaviruses induce a rapid inhibition of host-cell cap-dependent protein synthesis and this is mainly achieved through cleavage of eIF4G and/or dephosphorylation of 4E-BP1. In this study, the effect of calicivirus infection was examined on host-cell protein synthesis in order to determine whether they also induce host shut-off. We report that infection of cells with feline calicivirus (FCV) leads to the inhibition of cellular protein synthesis. This is accompanied by the cleavage of the eukaryotic translation initiation factors eIF4GI and eIF4GII in a manner reminiscent of that induced by picornaviruses. However, the cleavages occur at different sites. The potential mechanisms of these cleavage events and the implications for the translation of calicivirus mRNA are discussed.

Transcriptional and translational events during reovirus infection

1988 ◽  
Vol 66 (8) ◽  
pp. 803-812 ◽  
Author(s):  
Guy Lemay
Keyword(s):  
Protein Synthesis ◽  
Host Cell ◽  
Mrna Translation ◽  
Cell Membrane Permeability ◽  
Cell Protein ◽  
Viral Mrna ◽  
Genomic Rna ◽  
Host Cell Protein ◽  
Outer Capsid ◽  
Viral Genomic Rna

This short review focuses on the mechanisms involved in transcription and translation in mouse L cells infected with reoviruses. The viral genomic RNA (double-stranded), retained in the inner capsid following removal of the outer capsid of the infecting virion, is transcribed by a viral polymerase. The synthesized viral mRNA is blocked at the 5′ end by a cap structure similar to the cap structure of cellular mRNA but synthesized by the viral enzymes of the inner capsid. This viral mRNA is also used as the first strand and template for the synthesis of the second strand of viral genomic RNA; the newly replicated genome is retained in an inner capsid structure to generate the progeny subviral particles. These particles are active at the transcriptional level but do not synthesize the cap, owing to the absence of the guanylyltransferase activity involved in the formation of this structure. The uncapped mRNA, or late viral mRNA, constitutes the bulk part of viral mRNA. The transcription of the viral genome is finally arrested upon addition of outer capsid proteins to obtain a mature virion. During viral multiplication, there is a gradual inhibition of host-cell protein synthesis, concomitant with stimulation of late viral mRNA translation. The two phenomena are apparently distinct. Furthermore, the inhibition of host-cell protein synthesis has been shown to be dispensable for normal virus multiplication; however, it might accelerate it. The mechanisms responsible for inhibition are still unclear but might involve modifications in the activity of cellular cap-binding proteins. This last point suggests an analogy with poliovirus infection; the two systems are thus briefly compared. Possible significance of the absence of a poly(A) tract at the 3′ end of reovirus mRNA, in contrast to the occurrence of such a sequence at the end of cellular mRNA, is also examined. Different models involving cap discrimination, competition between mRNAs, or alteration of cell membrane permeability have been proposed to explain the events observed at the translational level in reovirus-infected cells. These different models are compared. Finally, recent data implicating the viral sigma 3 capsid protein in efficient translation of late viral mRNA are discussed.

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