Shut-Off of Host Protein Synthesis in Vaccinia-Virus-Infected Cells Exposed to Cordycepin. A Study in vitro

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.

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Characterization of vaccinia virus transcripts involved in selective inhibition of host protein synthesis

Virology ◽

10.1016/0042-6822(86)90334-x ◽

1986 ◽

Vol 148 (2) ◽

pp. 375-380 ◽

Cited By ~ 13

Author(s):

Rostom Bablanian ◽

George Coppola ◽

Paul S. Masters ◽

Amiya K. Banerjee

Keyword(s):

Protein Synthesis ◽

Vaccinia Virus ◽

Selective Inhibition ◽

Host Protein ◽

Host Protein Synthesis

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Selective blockage of initiation of host protein synthesis in RNA-virus-infected cells.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.72.4.1258 ◽

1975 ◽

Vol 72 (4) ◽

pp. 1258-1262 ◽

Cited By ~ 84

Author(s):

D. L. Nuss ◽

H. Oppermann ◽

G. Koch

Keyword(s):

Protein Synthesis ◽

Rna Virus ◽

Host Protein ◽

Infected Cells ◽

Host Protein Synthesis

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Inhibition of host protein synthesis by vaccinia virus: fate of cell mRNA and synthesis of small poly (A)-rich polyribonucleotides in the presence of actinomycin D.

Journal of Virology ◽

10.1128/jvi.16.1.34-42.1975 ◽

1975 ◽

Vol 16 (1) ◽

pp. 34-42 ◽

Cited By ~ 29

Author(s):

H Rosemond-Hornbeak ◽

B Moss

Keyword(s):

Protein Synthesis ◽

Vaccinia Virus ◽

Actinomycin D ◽

Host Protein ◽

Host Protein Synthesis

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Severe Acute Respiratory Syndrome Coronavirus nsp1 Suppresses Host Gene Expression, Including That of Type I Interferon, in Infected Cells

Journal of Virology ◽

10.1128/jvi.02472-07 ◽

2008 ◽

Vol 82 (9) ◽

pp. 4471-4479 ◽

Cited By ~ 182

Author(s):

Krishna Narayanan ◽

Cheng Huang ◽

Kumari Lokugamage ◽

Wataru Kamitani ◽

Tetsuro Ikegami ◽

...

Keyword(s):

Gene Expression ◽

Protein Synthesis ◽

Severe Acute Respiratory Syndrome ◽

Mrna Degradation ◽

Host Gene ◽

Host Protein ◽

Type I ◽

Host Gene Expression ◽

Infected Cells ◽

Host Protein Synthesis

ABSTRACT The severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 protein has unique biological functions that have not been described in the viral proteins of any RNA viruses; expressed SARS-CoV nsp1 protein has been found to suppress host gene expression by promoting host mRNA degradation and inhibiting translation. We generated an nsp1 mutant (nsp1-mt) that neither promoted host mRNA degradation nor suppressed host protein synthesis in expressing cells. Both a SARS-CoV mutant virus, encoding the nsp1-mt protein (SARS-CoV-mt), and a wild-type virus (SARS-CoV-WT) replicated efficiently and exhibited similar one-step growth kinetics in susceptible cells. Both viruses accumulated similar amounts of virus-specific mRNAs and nsp1 protein in infected cells, whereas the amounts of endogenous host mRNAs were clearly higher in SARS-CoV-mt-infected cells than in SARS-CoV-WT-infected cells, in both the presence and absence of actinomycin D. Further, SARS-CoV-WT replication strongly inhibited host protein synthesis, whereas host protein synthesis inhibition in SARS-CoV-mt-infected cells was not as efficient as in SARS-CoV-WT-infected cells. These data revealed that nsp1 indeed promoted host mRNA degradation and contributed to host protein translation inhibition in infected cells. Notably, SARS-CoV-mt infection, but not SARS-CoV-WT infection, induced high levels of beta interferon (IFN) mRNA accumulation and high titers of type I IFN production. These data demonstrated that SARS-CoV nsp1 suppressed host innate immune functions, including type I IFN expression, in infected cells and suggested that SARS-CoV nsp1 most probably plays a critical role in SARS-CoV virulence.

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Cleavage of Poly(A)-Binding Protein by Coxsackievirus 2A Protease In Vitro and In Vivo: Another Mechanism for Host Protein Synthesis Shutoff?

Journal of Virology ◽

10.1128/jvi.73.1.709-717.1999 ◽

1999 ◽

Vol 73 (1) ◽

pp. 709-717 ◽

Cited By ~ 131

Author(s):

Vaishali Kerekatte ◽

Brett D. Keiper ◽

Cornel Badorff ◽

Aili Cai ◽

Kirk U. Knowlton ◽

...

Keyword(s):

Protein Synthesis ◽

Translation Initiation ◽

Viral Protein ◽

Binding Protein ◽

Host Protein ◽

Viral Protein Synthesis ◽

2A Protease ◽

Host Protein Synthesis

ABSTRACT Infection of cells by picornaviruses of the rhinovirus, aphthovirus, and enterovirus groups results in the shutoff of host protein synthesis but allows viral protein synthesis to proceed. Although considerable evidence suggests that this shutoff is mediated by the cleavage of eukaryotic translation initiation factor eIF4G by sequence-specific viral proteases (2A protease in the case of coxsackievirus), several experimental observations are at variance with this view. Thus, the cleavage of other cellular proteins could contribute to the shutoff of host protein synthesis and stimulation of viral protein synthesis. Recent evidence indicates that the highly conserved 70-kDa cytoplasmic poly(A)-binding protein (PABP) participates directly in translation initiation. We have now found that PABP is also proteolytically cleaved during coxsackievirus infection of HeLa cells. The cleavage of PABP correlated better over time with the host translational shutoff and onset of viral protein synthesis than did the cleavage of eIF4G. In vitro experiments with purified rabbit PABP and recombinant human PABP as well as in vivo experiments withXenopus oocytes and recombinant Xenopus PABP demonstrate that the cleavage is catalyzed by 2A protease directly. N- and C-terminal sequencing indicates that cleavage occurs uniquely in human PABP at482VANTSTQTM↓GPRPAAAAAA500, separating the four N-terminal RNA recognition motifs (80%) from the C-terminal homodimerization domain (20%). The N-terminal cleavage product of PABP is less efficient than full-length PABP in restoring translation to a PABP-dependent rabbit reticulocyte lysate translation system. These results suggest that the cleavage of PABP may be another mechanism by which picornaviruses alter the rate and spectrum of protein synthesis.

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