Herpes Simplex Virus Virion Host Shutoff Attenuates Establishment of the Antiviral State
Tracy Jo Pasieka,Betty Lu,Seth D. Crosby,Kristine M. Wylie,Lynda A. Morrison,Diane E. Alexander,Vineet D. Menachery,David A. Leib,David A. Leib +8 more
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TL;DR: It is demonstrated that vhs-deficient viruses replicate to reduced levels in interferon (IFN)-primed cells and that this deficit has both IFN-dependent andIFN-independent components.
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Abstract: Herpes simplex virus mutants lacking the vhs protein are severely attenuated in animal models of pathogenesis and exhibit reduced growth in primary cell culture. As a result of these properties, viruses with vhs deleted have been proposed as live-attenuated vaccines. Despite these findings and their implications for vaccines, the mechanisms by which vhs promotes infection in cell culture and in vivo are not understood. In this study we demonstrate that vhs-deficient viruses replicate to reduced levels in interferon (IFN)-primed cells and that this deficit has both IFN-dependent and IFN-independent components. Furthermore, vhs-defective viruses induce increased and physiologically active levels of IFN, increased amounts of IFN-stimulated transcripts, and more phosphorylated eIF2alpha. In addition, we demonstrate greater accumulation of viral RNAs following infection with a vhs-deficient virus. This leads to the hypothesis that attenuation of viruses lacking vhs may be attributed to increased levels of double-stranded RNA, a potent pathogen-associated molecular pattern. Together these data show that vhs likely functions to reduce innate immune responses and thereby acts as a critical determinant of viral pathogenesis.
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References
Functional role of type I and type II interferons in antiviral defense.
Ulrike Müller,Ulrich Steinhoff,Luiz F. L. Reis,Silvio Hemmi,Jovan Pavlovic,Rolf M. Zinkernagel,Michel Aguet +6 more
TL;DR: Comparison of mice lacking either type I or type II IFN receptors showed that, at least in response to some viruses, both IFN systems are essential for antiviral defense and are functionally nonredundant.
2.5K
Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays
TL;DR: The results demonstrate the usefulness of oligonucleotide arrays in monitoring mammalian gene expression on a broad and unprecedented scale and provide insights into the basic mechanisms of IFN actions.
1.8K
Coping with stress: eIF2 kinases and translational control
TL;DR: While many of the genes induced by eIF2 phosphorylation are shared between different environmental stresses, eIF1 kinases function in conjunction with other stress-response pathways, such as those regulated by mitogen-activated protein kinases, to elicit gene expression programmes that are tailored for the specific stress condition.
1.3K
Double-Stranded RNA Is Produced by Positive-Strand RNA Viruses and DNA Viruses but Not in Detectable Amounts by Negative-Strand RNA Viruses
TL;DR: Investigation of the presence and localization of ds RNA in cells infected with a range of viruses, employing a dsRNA-specific antibody for immunofluorescence analysis revealed that significant amounts ofdsRNA can be detected for viruses with a genome consisting of positive-strand RNA, dsRNAs, or DNA; Surprisingly, however, no DsRNA signals were detected for negative-stranded RNA viruses.
989
Functional classification of interferon-stimulated genes identified using microarrays
Michael John de Veer,Michelle Holko,Michelle Holko,Mathias A E Frevel,Eldon M. Walker,Sandy D. Der,Jayashree M. Paranjape,Robert H. Silverman,Bryan R.G. Williams +8 more
TL;DR: This review focuses on new insights into the protein kinaseRNA‐regulated (PRKR) protein, which have been made possible with the availability of PRKR‐null mice, and focuses particularly on the functions of the ISGs identified by analyzing microarray data.
973