Giuseppe
Emeritus
[Source: PNAS, <cite cite="http://www.pnas.org/content/107/21/9837.short?rss=1">Inhibition of host translation by virus infection in vivo ? PNAS</cite>. Abstract, edited.]
Inhibition of host translation by virus infection in vivo
Ren? Toribio and Iv?n Ventoso
Author Affiliations:
Departamento de Biolog?a Molecular and Centro de Biolog?a Molecular ?Severo Ochoa,? Consejo Superior de Investigaciones Cientificas?Universidad Aut?noma de Madrid, Universidad Aut?noma de Madrid, Cantoblanco 28049 Madrid, Spain
Edited by Diane E. Griffin, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, and approved April 19, 2010 (received for review March 26, 2010)
Abstract
Infection of cultured cells with lytic animal viruses often results in the selective inhibition of host protein synthesis, whereas viral mRNA is efficiently translated under these circumstances. This phenomenon, known as ?shut off,? has been well described at the molecular level for some viruses, but there is not yet any direct or indirect evidence supporting the idea that it also should operate in animals infected with viruses. To address this issue, we constructed recombinant Sindbis virus (SV)-expressing reporter mRNA, the translation of which is sensitive or resistant to virus-induced shut off. As found in cultured cells, replication of SV in mouse brain was associated with a strong phosphorylation of eukaryotic initiation factor (eIF2) that prevented translation of reporter mRNA (luciferase and EGFP). Translation of these reporters was restored in vitro, in vivo, and ex vivo when a viral RNA structure, termed downstream hairpin loop, present in viral 26S mRNA, was placed at the 5′ end of reporter mRNAs. By comparing the expression of shut off-sensitive and -resistant reporters, we unequivocally concluded that replication of SV in animal tissues is associated with a profound inhibition of nonviral mRNA translation. A strategy as simple as that followed here might be applicable to other viruses to evaluate their interference on host translation in infected animals.
* eukaryotic initiation factor-2 phosphorylation
* dsRNA-dependent protein kinase
* Sindbis
Footnotes:
To whom correspondence should be addressed. E-mail: iventoso@cbm.uam.es.
Author contributions: R.T. and I.V. designed research; R.T. performed research; R.T. analyzed data; and I.V. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1004110107/-/DCSupplemental.
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Inhibition of host translation by virus infection in vivo
Ren? Toribio and Iv?n Ventoso
Author Affiliations:
Departamento de Biolog?a Molecular and Centro de Biolog?a Molecular ?Severo Ochoa,? Consejo Superior de Investigaciones Cientificas?Universidad Aut?noma de Madrid, Universidad Aut?noma de Madrid, Cantoblanco 28049 Madrid, Spain
Edited by Diane E. Griffin, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, and approved April 19, 2010 (received for review March 26, 2010)
Abstract
Infection of cultured cells with lytic animal viruses often results in the selective inhibition of host protein synthesis, whereas viral mRNA is efficiently translated under these circumstances. This phenomenon, known as ?shut off,? has been well described at the molecular level for some viruses, but there is not yet any direct or indirect evidence supporting the idea that it also should operate in animals infected with viruses. To address this issue, we constructed recombinant Sindbis virus (SV)-expressing reporter mRNA, the translation of which is sensitive or resistant to virus-induced shut off. As found in cultured cells, replication of SV in mouse brain was associated with a strong phosphorylation of eukaryotic initiation factor (eIF2) that prevented translation of reporter mRNA (luciferase and EGFP). Translation of these reporters was restored in vitro, in vivo, and ex vivo when a viral RNA structure, termed downstream hairpin loop, present in viral 26S mRNA, was placed at the 5′ end of reporter mRNAs. By comparing the expression of shut off-sensitive and -resistant reporters, we unequivocally concluded that replication of SV in animal tissues is associated with a profound inhibition of nonviral mRNA translation. A strategy as simple as that followed here might be applicable to other viruses to evaluate their interference on host translation in infected animals.
* eukaryotic initiation factor-2 phosphorylation
* dsRNA-dependent protein kinase
* Sindbis
Footnotes:
To whom correspondence should be addressed. E-mail: iventoso@cbm.uam.es.
Author contributions: R.T. and I.V. designed research; R.T. performed research; R.T. analyzed data; and I.V. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1004110107/-/DCSupplemental.
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