scholarly journals Influenza Virus mRNA Translation Revisited: Is the eIF4E Cap-Binding Factor Required for Viral mRNA Translation?

2007 ◽  
Vol 81 (22) ◽  
pp. 12427-12438 ◽  
Author(s):  
Idoia Burgui ◽  
Emilio Yángüez ◽  
Nahum Sonenberg ◽  
Amelia Nieto
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Host Cell ◽  
Influenza Virus Infection ◽  
Mrna Translation ◽  
Cell Protein ◽  
Viral Mrna ◽  
Viral Sequence ◽  
Viral Polymerase ◽  
Viral Mrnas

ABSTRACT Influenza virus mRNAs bear a short capped oligonucleotide sequence at their 5′ ends derived from the host cell pre-mRNAs by a “cap-snatching” mechanism, followed immediately by a common viral sequence. At their 3′ ends, they contain a poly(A) tail. Although cellular and viral mRNAs are structurally similar, influenza virus promotes the selective translation of its mRNAs despite the inhibition of host cell protein synthesis. The viral polymerase performs the cap snatching and binds selectively to the 5′ common viral sequence. As viral mRNAs are recognized by their own cap-binding complex, we tested whether viral mRNA translation occurs without the contribution of the eIF4E protein, the cellular factor required for cap-dependent translation. Here, we show that influenza virus infection proceeds normally in different situations of functional impairment of the eIF4E factor. In addition, influenza virus polymerase binds to translation preinitiation complexes, and furthermore, under conditions of decreased eIF4GI association to cap structures, an increase in eIF4GI binding to these structures was found upon influenza virus infection. This is the first report providing evidence that influenza virus mRNA translation proceeds independently of a fully active translation initiation factor (eIF4E). The data reported are in agreement with a role of viral polymerase as a substitute for the eIF4E factor for viral mRNA translation.

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.

scholarly journals Regulation of mRNA translation machinery in influenza virus infection

2019 ◽  
Vol 92 (0) ◽  
pp. 1-YIA-10
Author(s):  
Masami Shiimori ◽  
Yu Ichida ◽  
Yuki Fujiwara ◽  
Midori Hoshizaki ◽  
Keiji Kuba ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Mrna Translation ◽  
Translation Machinery

Translational control by influenza virus: suppression of the kinase that phosphorylates the alpha subunit of initiation factor eIF-2 and selective translation of influenza viral mRNAs

1986 ◽  
Vol 6 (5) ◽  
pp. 1741-1750
Author(s):  
M G Katze ◽  
B M Detjen ◽  
B Safer ◽  
R M Krug
Keyword(s):  
Protein Synthesis ◽  
Influenza Virus ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Alpha Subunit ◽  
Viral Mrna ◽  
Viral Mrnas ◽  
Double Stranded Rna ◽  
Selective Translation ◽  
Infected Cells

Selective translation of influenza viral mRNAs occurs after influenza virus superinfection of cells infected with the VAI RNA-negative adenovirus mutant dl331 (M. G. Katze, Y.-T. Chen, and R. M. Krug, Cell 37:483-490, 1984). Cell extracts from these doubly infected cells catalyze the initiation of essentially only influenza viral protein synthesis, reproducing the in vivo situation. This selective translation is correlated with a 5- to 10-fold suppression of the dl331-induced kinase that phosphorylates the alpha subunit of eucaryotic initiation factor eIF-2. This strongly suggests that influenza virus encodes a gene product that, analogous to the adenoviral VAI RNA, prevents the shutdown of overall protein synthesis caused by an eIF-2 alpha kinase turned on by viral infection. Adenoviral mRNA translation was restored to the extract from the doubly infected cells by the addition of the guanine nucleotide exchange factor eIF-2B, which is responsible for the normal recycling of eIF-2 during protein synthesis. This indicates that the residual kinase in the doubly infected cells leads to a limitation in functional (nonsequestered) eIF-2B and hence functional (GTP-containing) eIF-2 and that under these conditions influenza viral mRNAs are selectively translated over adenoviral mRNAs. Addition of double-stranded RNA to the extracts from these cells restored the eIF-2 alpha kinase to a level approaching that seen in extracts from cells infected with dl331 alone and caused the inhibition of influenza viral mRNA translation. This suggests that the putative influenza viral gene product acts against the double-stranded RNA activation of the kinase and indicates that influenza viral mRNA translation is also linked to the level of functional eIF-2. Our results thus indicate that a limitation in functional eIF-2 which causes a nonspecific reduction in the rate of initiation of protein synthesis results in the preferential translation of the better mRNAs (influenza viral mRNAs) at the expense of the poorer mRNAs (adenoviral mRNAs).

scholarly journals Extreme heterogeneity of influenza virus infection in single cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Alistair B Russell ◽  
Cole Trapnell ◽  
Jesse D Bloom
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Single Cells ◽  
Influenza Virus Infection ◽  
Viral Gene ◽  
Viral Mrnas ◽  
Cellular Genes ◽  
Infected Cells ◽  
Cell Variation

Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.

scholarly journals Bivalent role of the phosphatidylinositol-3-kinase (PI3K) during influenza virus infection and host cell defence

2006 ◽  
Vol 8 (8) ◽  
pp. 1336-1348 ◽  
Author(s):  
Christina Ehrhardt ◽  
Henju Marjuki ◽  
Thorsten Wolff ◽  
Bernd Nurnberg ◽  
Oliver Planz ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Host Cell ◽  
Influenza Virus Infection ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

Hijacking of the host-cell response and translational control during influenza virus infection

2006 ◽  
Vol 119 (1) ◽  
pp. 111-120 ◽  
Author(s):  
John C. Kash ◽  
Alan G. Goodman ◽  
Marcus J. Korth ◽  
Michael G. Katze
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Host Cell ◽  
Translational Control ◽  
Cell Response ◽  
Influenza Virus Infection ◽  
Host Cell Response

scholarly journals Translational control by influenza virus: suppression of the kinase that phosphorylates the alpha subunit of initiation factor eIF-2 and selective translation of influenza viral mRNAs.

1986 ◽  
Vol 6 (5) ◽  
pp. 1741-1750 ◽  
Author(s):  
M G Katze ◽  
B M Detjen ◽  
B Safer ◽  
R M Krug
Keyword(s):  
Protein Synthesis ◽  
Influenza Virus ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Alpha Subunit ◽  
Viral Mrna ◽  
Viral Mrnas ◽  
Double Stranded Rna ◽  
Selective Translation ◽  
Infected Cells

Selective translation of influenza viral mRNAs occurs after influenza virus superinfection of cells infected with the VAI RNA-negative adenovirus mutant dl331 (M. G. Katze, Y.-T. Chen, and R. M. Krug, Cell 37:483-490, 1984). Cell extracts from these doubly infected cells catalyze the initiation of essentially only influenza viral protein synthesis, reproducing the in vivo situation. This selective translation is correlated with a 5- to 10-fold suppression of the dl331-induced kinase that phosphorylates the alpha subunit of eucaryotic initiation factor eIF-2. This strongly suggests that influenza virus encodes a gene product that, analogous to the adenoviral VAI RNA, prevents the shutdown of overall protein synthesis caused by an eIF-2 alpha kinase turned on by viral infection. Adenoviral mRNA translation was restored to the extract from the doubly infected cells by the addition of the guanine nucleotide exchange factor eIF-2B, which is responsible for the normal recycling of eIF-2 during protein synthesis. This indicates that the residual kinase in the doubly infected cells leads to a limitation in functional (nonsequestered) eIF-2B and hence functional (GTP-containing) eIF-2 and that under these conditions influenza viral mRNAs are selectively translated over adenoviral mRNAs. Addition of double-stranded RNA to the extracts from these cells restored the eIF-2 alpha kinase to a level approaching that seen in extracts from cells infected with dl331 alone and caused the inhibition of influenza viral mRNA translation. This suggests that the putative influenza viral gene product acts against the double-stranded RNA activation of the kinase and indicates that influenza viral mRNA translation is also linked to the level of functional eIF-2. Our results thus indicate that a limitation in functional eIF-2 which causes a nonspecific reduction in the rate of initiation of protein synthesis results in the preferential translation of the better mRNAs (influenza viral mRNAs) at the expense of the poorer mRNAs (adenoviral mRNAs).

scholarly journals Extreme heterogeneity of influenza virus infection in single cells

2017 ◽  
Author(s):  
Alistair B. Russell ◽  
Cole Trapnell ◽  
Jesse D. Bloom
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Single Cells ◽  
Influenza Virus Infection ◽  
Viral Gene ◽  
Viral Mrnas ◽  
Cellular Genes ◽  
Gene Transcripts ◽  
Infected Cells

AbstractViral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of Influenza virus infection. We 1nd extremely wide cell-to-cell variation in production of viral gene transcripts – viral transcripts compose less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, and this gene absence partially explains variation in viral transcriptional load. Despite variation in total viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.

scholarly journals Metabolism and expression of RNA polymerase II transcripts in influenza virus-infected cells.

1984 ◽  
Vol 4 (10) ◽  
pp. 2198-2206 ◽  
Author(s):  
M G Katze ◽  
R M Krug
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Rna Polymerase ◽  
Host Cell ◽  
Rna Polymerase Ii ◽  
Hela Cells ◽  
Influenza Virus Infection ◽  
Beta Actin ◽  
Chicken Embryo Fibroblasts

Influenza virus infection has adverse effects on the metabolism of two representative RNA polymerase II transcripts in chicken embryo fibroblasts, those coding for beta-actin and for avian leukosis virus (ALV) proteins. Proviral ALV DNA was integrated into host cell DNA by prior infection with ALV. Within 1 h after influenza virus infection, the rate of transcription of beta-actin and ALV sequences decreased 40 to 60%, as determined by labeling the cells for 5 min with [3H]uridine and by in vitro, runoff assays with isolated nuclei. The transcripts that continued to be synthesized did not appear in the cytoplasm as mature mRNAs, and the kinetics of labeling of these transcripts strongly suggest that they were degraded in the nucleus. By S1 endonuclease assay, it was confirmed that nuclear ALV transcripts disappeared very early after infection, already decreasing ca. 80% by 1 h postinfection. A plausible explanation for this nuclear degradation is that the viral cap-dependent endonuclease in the nucleus cleaves the 5' ends of new polymerase II transcripts, rendering the resulting decapped RNAs susceptible to hydrolysis by cellular nucleases. In contrast to the nuclear transcripts, cytoplasmic beta-actin and ALV mRNAs, which are synthesized before infection, were more stable and did not decrease in amount until after 3 h postinfection. Similar stability of cytoplasmic host cell mRNAs was observed in infected HeLa cells, in which the levels of actin mRNA and two HeLa cell mRNAs (pHe 7 and pHe 28) remained at undiminished levels for 3 h of infection and decreased only slightly by 4.5 h postinfection. The cytoplasmic actin and pHe 7 mRNAs isolated from infected HeLa cells were shown to be translated in reticulocyte extracts in vitro, indicating that host mRNAs were not inactivated by a virus-induced modification. Despite the continued presence of high levels of functional host cell mRNAs, host cell protein synthesis was effectively shut off by about 3 h postinfection in both chicken embryo fibroblasts and HeLa cells. These results are consistent with the establishment of an influenza virus-specific translational system that selectively translates viral and not host mRNAs.

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