scholarly journals SARS-CoV-2 utilizes a multipronged strategy to suppress host protein synthesis

2020 ◽  
Author(s):  
Yaara Finkel ◽  
Avi Gluck ◽  
Roni Winkler ◽  
Aharon Nachshon ◽  
Orel Mizrahi ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Cellular Protein ◽  
Ribosome Profiling ◽  
Innate Immune ◽  
Host Protein ◽  
Immune Genes ◽  
Mrna Pool ◽  
Cellular Mrnas ◽  
Infected Cells ◽  
Innate Immune Genes

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 19 (COVID-19) pandemic. Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis and its ability to antagonize innate immune responses. Here, we use RNA-sequencing and ribosome profiling along SARS-CoV-2 infection and comprehensively define the mechanisms that are utilized by SARS-CoV-2 to shutoff cellular protein synthesis. We show SARS-CoV-2 infection leads to a global reduction in translation but that viral transcripts are not preferentially translated. Instead, we reveal that infection leads to accelerated degradation of cytosolic cellular mRNAs which facilitates viral takeover of the mRNA pool in infected cells. Moreover, we show that the translation of transcripts whose expression is induced in response to infection, including innate immune genes, is impaired, implying infection prevents newly transcribed cellular mRNAs from accessing the ribosomes. Overall, our results uncover the multipronged strategy employed by SARS-CoV-2 to commandeer the translation machinery and to suppress host defenses.

Effect of adenovirus on metabolism of specific host mRNAs: transport control and specific translational discrimination

1983 ◽  
Vol 3 (7) ◽  
pp. 1212-1221 ◽  
Author(s):  
A Babich ◽  
L T Feldman ◽  
J R Nevins ◽  
J E Darnell ◽  
C Weinberger
Keyword(s):  
Protein Synthesis ◽  
Host Cell ◽  
Cellular Protein ◽  
Host Protein ◽  
Cell Protein ◽  
Viral Mrna ◽  
Initiation Of Translation ◽  
Viral Mutant ◽  
Cellular Mrnas ◽  
Cellular Protein Synthesis

We have studied the adenovirus-induced inhibition of host cell protein synthesis and the effect of infection on the overall metabolism of host cell mRNA during the late phase of adenovirus infection by following the fate of a number of cellular mRNAs complementary to specific cloned DNA segments. At a time in infection when the rate of total cellular protein synthesis is drastically (greater than 90%) reduced, transcription of specific cellular genes is undiminished. However, the transport of newly synthesized cellular mRNA to the cytoplasm is greatly decreased. This decreased appearance of new mRNA in the cytoplasm cannot account for the observed cessation of cell specific protein synthesis, however, since the concentration of several preexisting cellular mRNAs, including the mRNA for actin, remains unchanged throughout the course of infection. The preexisting mRNA is intact, capped, and functional as judged by its ability to direct protein synthesis in vitro in a cap-dependent fashion. The interruption in host translation appears to operate at the level of initiation directly, since we find that fewer ribosomes are associated with a given cellular mRNA after infection than before infection. Furthermore, the in vivo inhibition of cellular protein synthesis does not appear to be the result of competition with viral mRNA, since conditions which prevent the efficient initiation of translation of viral mRNA (infection with a viral mutant) do not result in the recovery of cell translation. Thus, it appears that a late adenovirus gene product directly mediates a shutoff of host protein synthesis.

scholarly journals Effect of adenovirus on metabolism of specific host mRNAs: transport control and specific translational discrimination.

1983 ◽  
Vol 3 (7) ◽  
pp. 1212-1221 ◽  
Author(s):  
A Babich ◽  
L T Feldman ◽  
J R Nevins ◽  
J E Darnell ◽  
C Weinberger
Keyword(s):  
Protein Synthesis ◽  
Host Cell ◽  
Cellular Protein ◽  
Host Protein ◽  
Cell Protein ◽  
Viral Mrna ◽  
Initiation Of Translation ◽  
Viral Mutant ◽  
Cellular Mrnas ◽  
Cellular Protein Synthesis

We have studied the adenovirus-induced inhibition of host cell protein synthesis and the effect of infection on the overall metabolism of host cell mRNA during the late phase of adenovirus infection by following the fate of a number of cellular mRNAs complementary to specific cloned DNA segments. At a time in infection when the rate of total cellular protein synthesis is drastically (greater than 90%) reduced, transcription of specific cellular genes is undiminished. However, the transport of newly synthesized cellular mRNA to the cytoplasm is greatly decreased. This decreased appearance of new mRNA in the cytoplasm cannot account for the observed cessation of cell specific protein synthesis, however, since the concentration of several preexisting cellular mRNAs, including the mRNA for actin, remains unchanged throughout the course of infection. The preexisting mRNA is intact, capped, and functional as judged by its ability to direct protein synthesis in vitro in a cap-dependent fashion. The interruption in host translation appears to operate at the level of initiation directly, since we find that fewer ribosomes are associated with a given cellular mRNA after infection than before infection. Furthermore, the in vivo inhibition of cellular protein synthesis does not appear to be the result of competition with viral mRNA, since conditions which prevent the efficient initiation of translation of viral mRNA (infection with a viral mutant) do not result in the recovery of cell translation. Thus, it appears that a late adenovirus gene product directly mediates a shutoff of host protein synthesis.

1080 Milk yield genotype impacts expression of hepatic innate immune genes during the transition period in Holsteins

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 518-518
Author(s):  
G. T. Cousillas ◽  
W. J. Weber ◽  
B. Walcheck ◽  
D. E. Kerr ◽  
T. H. Elsasser ◽  
...  
Keyword(s):  
Milk Yield ◽  
Transition Period ◽  
Innate Immune ◽  
Immune Genes ◽  
Innate Immune Genes

Flagellin induces innate immune genes in bronchial epithelial cells in vivo: Role of TET2

2021 ◽  
Author(s):  
Wanhai Qin ◽  
Xanthe Brands ◽  
Cornelis Veer ◽  
Alex F. Vos ◽  
Brendon P. Scicluna ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Innate Immune ◽  
Bronchial Epithelial ◽  
Immune Genes ◽  
Innate Immune Genes

microRNA-252 and FoxO repress inflammaging by a dual inhibitory mechanism on Dawdle mediated TGF-β pathway in Drosophila

Genetics ◽  
2021 ◽  
Author(s):  
Xiaofen Wu ◽  
Kongyan Niu ◽  
Xiaofan Wang ◽  
Jing Zhao ◽  
Han Wang ◽  
...  
Keyword(s):  
Cell Types ◽  
Innate Immune ◽  
Low Grade ◽  
Sequencing Analysis ◽  
Immune Genes ◽  
Healthy Longevity ◽  
Muscle Tissues ◽  
Distinct Cell ◽  
A Cell ◽  
Innate Immune Genes

Abstract Inflammaging refers to low-grade, chronically activated innate immunity that has deleterious effects on healthy lifespan. However, little is known about the intrinsic signaling pathway that elicits innate immune genes during aging. Here using Drosophila melanogaster, we profile the microRNA targetomes in young and aged animals, and reveal Dawdle (Daw), an activin-like ligand of the TGF-β pathway, as a physiological target of microRNA-252 (miR-252). We show that miR-252 cooperates with Forkhead box O (FoxO), a conserved transcriptional factor implicated in aging, to repress Daw. Unopposed Daw triggers hyper activation of innate immune genes coupled with a decline in organismal survival. Using adult muscle tissues, single-cell sequencing analysis describes that Daw and its downstream innate immune genes are expressed in distinct cell types, suggesting a cell non-autonomous mode of regulation. We further determine the genetic cascade by which Daw signaling leads to increased Kenny/IKKγ protein, which in turn activates Relish/NF-κB protein and consequentially innate immune genes. Finally, transgenic increase of miR-252 and FoxO pathway factors in wild-type Drosophila extends lifespan and mitigates the induction of innate immune genes in aging. Together, we propose that miR-252 and FoxO promote healthy longevity by cooperative inhibition on Daw mediated inflammaging.

scholarly journals Inhibition of Host Protein Synthesis and Degradation of Cellular mRNAs During Infection by Influenza and Herpes Simplex Virus

1982 ◽  
Vol 2 (12) ◽  
pp. 1644-1648 ◽  
Author(s):  
S. C. Inglis
Keyword(s):  
Protein Synthesis ◽  
Blot Hybridization ◽  
Host Protein ◽  
Cell Protein ◽  
Cellular Genes ◽  
Cellular Mrnas ◽  
The Stability ◽  
Simplex Virus ◽  
Host Protein Synthesis ◽  
Synthesis And Degradation

Cloned DNA copies of two cellular genes were used to monitor, by blot hybridization, the stability of particular cell mRNAs after infection by influenza virus and herpesvirus. The results indicated that the inhibition of host cell protein synthesis that accompanied infection by each virus could be explained by a reduction in the amounts of cellular mRNAs in the cytoplasm, and they suggested that this decrease was due to virus-mediated mRNA degradation.

scholarly journals Modulatory upregulation of an insulin peptide gene by different pathogens in C. elegans

2017 ◽  
Author(s):  
Song-Hua Lee ◽  
Shizue Omi ◽  
Nishant Thakur ◽  
Clara Taffoni ◽  
Jérôme Belougne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Signaling ◽  
Kinase Inhibitor ◽  
Innate Immune ◽  
Immune Genes ◽  
C Elegans ◽  
Intestinal Infections ◽  
Innate Immune Genes ◽  
Peptide Gene ◽  
Complex Manner

ABSTRACTWhen an animal is infected, its innate immune response needs to be tightly regulated across tissues and coordinated with other aspects of organismal physiology. Previous studies with Caenorhabditis elegans have demonstrated that insulin-like peptide genes are differentially expressed in response to different pathogens. They represent prime candidates for conveying signals between tissues upon infection. Here, we focused on one such gene, ins-11 and its potential role in mediating cross-tissue regulation of innate immune genes. While diverse bacterial intestinal infections can trigger the up-regulation of ins-11 in the intestine, we show that epidermal infection with the fungus Drechmeria coniospora triggers an upregulation of ins-11 in the epidermis. Using the Shigella virulence factor OpsF, a MAP kinase inhibitor, we found that in both cases, ins-11 expression is controlled cell autonomously by p38 MAPK, but via distinct transcription factors, STA-2/STAT in the epidermis and HLH-30/TFEB in the intestine. We established that ins-11, and the insulin signaling pathway more generally, are not involved in the regulation of antimicrobial peptide gene expression in the epidermis. The up-regulation of ins-11 in the epidermis does, however, affect intestinal gene expression in a complex manner, and has a deleterious effect on longevity. These results support a model in which insulin signaling, via ins-11, contributes to the coordination of the organismal response to infection, influencing the allocation of resources in an infected animal.

Modification of protein synthesis initiation factors and the shut-off of host protein synthesis in adenovirus-infected cells

Virology ◽  
1989 ◽  
Vol 168 (1) ◽  
pp. 112-118 ◽  
Author(s):  
Robert P. O'Malley ◽  
Roger F. Duncan ◽  
John W.B. Hershey ◽  
Michael B. Mathews
Keyword(s):  
Protein Synthesis ◽  
Host Protein ◽  
Initiation Factors ◽  
Infected Cells ◽  
Protein Synthesis Initiation ◽  
Host Protein Synthesis

scholarly journals The dynamics of coiled bodies in the nucleus of adenovirus-infected cells.

1996 ◽  
Vol 7 (7) ◽  
pp. 1137-1151 ◽  
Author(s):  
L Rebelo ◽  
F Almeida ◽  
C Ramos ◽  
K Bohmann ◽  
A I Lamond ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Hela Cells ◽  
Host Protein ◽  
Coiled Body ◽  
Adenovirus Infection ◽  
Protein Synthesis Inhibitors ◽  
Coiled Bodies ◽  
Infected Cells ◽  
Host Protein Synthesis ◽  
Small Nuclear Ribonucleoproteins

The coiled body is a specific intranuclear structure of unknown function that is enriched in splicing small nuclear ribonucleoproteins (snRNPs). Because adenoviruses make use of the host cell-splicing machinery and subvert the normal subnuclear organization, we initially decided to investigate the effect of adenovirus infection on the coiled body. The results indicate that adenovirus infection induces the disassembly of coiled bodies and that this effect is probably secondary to the block of host protein synthesis induced by the virus. Furthermore, coiled bodies are shown to be very labile structures, with a half-life of approximately 2 h after treatment of HeLa cells with protein synthesis inhibitors. After blocking of protein synthesis, p80 coilin was detected in numerous microfoci that do not concentrate snRNP. These structures may represent precursor forms of the coiled body, which goes through a rapid cycle of assembly/disassembly in the nucleus and requires ongoing protein synthesis to reassemble.

Sign in / Sign up

Export Citation Format

Share Document