scholarly journals Herpes Simplex Virus Virion Host Shutoff Protein Is Stimulated by Translation Initiation Factors eIF4B and eIF4H

2004 ◽  
Vol 78 (9) ◽  
pp. 4684-4699 ◽  
Author(s):  
Rosalyn C. Doepker ◽  
Wei-Li Hsu ◽  
Holly A. Saffran ◽  
James R. Smiley
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Translation Initiation ◽  
Encephalomyocarditis Virus ◽  
Translation Initiation Factor ◽  
Rnase Activity ◽  
Virion Host Shutoff ◽  
Virion Host Shutoff Protein ◽  
Host Shutoff ◽  
Simplex Virus

ABSTRACT The virion host shutoff protein (vhs) of herpes simplex virus triggers accelerated degradation of cellular and viral mRNAs while sparing other cytoplasmic RNA species. Previous work has shown that vhs forms a complex with translation initiation factor eIF4H, which displays detectable RNase activity in the absence of other viral or host proteins. However, the contributions of eIF4H and other host factors to the activity and mRNA targeting properties of vhs have not yet been directly examined. An earlier report from our laboratory demonstrated that rabbit reticulocyte lysate (RRL) contains one or more factors that strongly stimulate the RNase activity of vhs produced in Saccharomyces cerevisiae. We report here that such yeast extracts display significant vhs-dependent RNase activity in the absence of mammalian factors. This activity differs from that displayed by vhs generated in RRL in that it is not targeted to the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES). Activity was strongly enhanced by the addition of RRL, eIF4H, or the related translation factor eIF4B. RRL also reconstituted strong targeting to the EMCV IRES, resulting in a major change in the RNA cleavage pattern. In contrast, eIF4H and eIF4B did not reconstitute IRES-directed targeting. These data indicate that eIF4B and 4H stimulate the nuclease activity of vhs, and they provide evidence that additional mammalian factors are required for targeting to the EMCV IRES.

scholarly journals mRNA Decay during Herpes Simplex Virus (HSV) Infections: Protein-Protein Interactions Involving the HSV Virion Host Shutoff Protein and Translation Factors eIF4H and eIF4A

2005 ◽  
Vol 79 (15) ◽  
pp. 9651-9664 ◽  
Author(s):  
Pinghui Feng ◽  
David N. Everly ◽  
G. Sullivan Read
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Translation Initiation ◽  
Mammalian Cells ◽  
Translation Initiation Factor ◽  
Site Directed Mutagenesis ◽  
Initiation Factor ◽  
Virion Host Shutoff ◽  
Host Shutoff ◽  
Simplex Virus

ABSTRACT During lytic infections, the virion host shutoff (Vhs) protein of herpes simplex virus accelerates the degradation of both host and viral mRNAs. In so doing, it helps redirect the cell from host to viral protein synthesis and facilitates the sequential expression of different viral genes. Vhs interacts with the cellular translation initiation factor eIF4H, and several point mutations that abolish its mRNA degradative activity also abrogate its ability to bind eIF4H. In addition, a complex containing bacterially expressed Vhs and a glutathione S-transferase (GST)-eIF4H fusion protein has RNase activity. eIF4H shares a region of sequence homology with eIF4B, and it appears to be functionally similar in that both stimulate the RNA helicase activity of eIF4A, a component of the mRNA cap-binding complex eIF4F. We show that eIF4H interacts physically with eIF4A in the yeast two-hybrid system and in GST pull-down assays and that the two proteins can be coimmunoprecipitated from mammalian cells. Vhs also interacts with eIF4A in GST pull-down and coimmunoprecipitation assays. Site-directed mutagenesis of Vhs and eIF4H revealed residues of each that are important for their mutual interaction, but not for their interaction with eIF4A. Thus, Vhs, eIF4H, and eIF4A comprise a group of proteins, each of which is able to interact directly with the other two. Whether they interact simultaneously as a tripartite complex or sequentially is unclear. The data suggest a mechanism for linking the degradation of an mRNA to its translation and for targeting Vhs to mRNAs and to regions of translation initiation.

scholarly journals Herpes Simplex Virus 1 Counteracts Viperin via Its Virion Host Shutoff Protein UL41

2014 ◽  
Vol 88 (20) ◽  
pp. 12163-12166 ◽  
Author(s):  
G. Shen ◽  
K. Wang ◽  
S. Wang ◽  
M. Cai ◽  
M.-l. Li ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus 1 ◽  
Virion Host Shutoff ◽  
Virion Host Shutoff Protein ◽  
Host Shutoff ◽  
Simplex Virus

scholarly journals Herpes simplex virus VP16 forms a complex with the virion host shutoff protein vhs.

1994 ◽  
Vol 68 (4) ◽  
pp. 2339-2346 ◽  
Author(s):  
C A Smibert ◽  
B Popova ◽  
P Xiao ◽  
J P Capone ◽  
J R Smiley
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virion Host Shutoff ◽  
Virion Host Shutoff Protein ◽  
Host Shutoff ◽  
Simplex Virus

scholarly journals Herpes Simplex Virus 2 Virion Host Shutoff Endoribonuclease Activity Is Required To Disrupt Stress Granule Formation

2016 ◽  
Vol 90 (17) ◽  
pp. 7943-7955 ◽  
Author(s):  
Renée L. Finnen ◽  
Mingzhao Zhu ◽  
Jing Li ◽  
Daniel Romo ◽  
Bruce W. Banfield
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Stress Granules ◽  
Granule Formation ◽  
Virion Host Shutoff ◽  
Virion Host Shutoff Protein ◽  
Host Shutoff ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Endoribonuclease Activity

ABSTRACTWe previously established that cells infected with herpes simplex virus 2 (HSV-2) are disrupted in their ability to form stress granules (SGs) in response to oxidative stress and that this disruption is mediated by virion host shutoff protein (vhs), a virion-associated endoribonuclease. Here, we test the requirement for vhs endoribonuclease activity in disruption of SG formation. We analyzed the ability of HSV-2 vhs carrying the point mutation D215N, which ablates its endoribonuclease activity, to disrupt SG formation in both transfected and infected cells. We present evidence that ablation of vhs endoribonuclease activity results in defects in vhs-mediated disruption of SG formation. Furthermore, we demonstrate that preformed SGs can be disassembled by HSV-2 infection in a manner that requires vhs endoribonuclease activity and that, befitting this ability to promote SG disassembly, vhs is able to localize to SGs. Together these data indicate that endoribonuclease activity must be maintained in order for vhs to disrupt SG formation. We propose a model whereby vhs-mediated destruction of SG mRNA promotes SG disassembly and may also prevent SG assembly.IMPORTANCEStress granules (SGs) are transient cytoplasmic structures that form when a cell is exposed to stress. SGs are emerging as potential barriers to viral infection, necessitating a more thorough understanding of their basic biology. We identified virion host shutoff protein (vhs) as a herpes simplex virus 2 (HSV-2) protein capable of disrupting SG formation. As mRNA is a central component of SGs and the best-characterized activity of vhs is as an endoribonuclease specific for mRNAin vivo, we investigated the requirement for vhs endoribonuclease activity in disruption of SG formation. Our studies demonstrate that endoribonuclease activity is required for vhs to disrupt SG formation and, more specifically, that SG disassembly can be driven by vhs endoribonuclease activity. Notably, during the course of these studies we discovered that there is an ordered departure of SG components during their disassembly and, furthermore, that vhs itself has the capacity to localize to SGs.

scholarly journals The Virion Host Shutoff Endonuclease (UL41) of Herpes Simplex Virus Interacts with the Cellular Cap-Binding Complex eIF4F

2010 ◽  
Vol 84 (13) ◽  
pp. 6886-6890 ◽  
Author(s):  
Heidi G. Page ◽  
G. Sullivan Read
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Translation Initiation ◽  
Viral Mrnas ◽  
Translation Factors ◽  
Virion Host Shutoff ◽  
Cap Binding Complex ◽  
Host Shutoff ◽  
Simplex Virus

ABSTRACT The herpes simplex virus Vhs endonuclease degrades host and viral mRNAs. Isolated Vhs cuts any RNA at many sites. Yet, within cells, it targets mRNAs and cuts at preferred sites, including regions of translation initiation. Previous studies have shown that Vhs binds the translation factors eIF4A and eIF4H. Here, we show that Vhs binds the cap-binding complex eIF4F. Association with eIF4F correlated with the ability of Vhs to bind eIF4A but not eIF4H. All Vhs proteins that degrade mRNAs associated with eIF4F. However, simply tethering an active endonuclease to eIF4F is not sufficient to degrade mRNAs. Binding to eIF4H may also be required.

scholarly journals Deletion of the Virion Host Shutoff Protein (vhs) from Herpes Simplex Virus (HSV) Relieves the Viral Block to Dendritic Cell Activation: Potential of vhs− HSV Vectors for Dendritic Cell-Mediated Immunotherapy

2003 ◽  
Vol 77 (6) ◽  
pp. 3768-3776 ◽  
Author(s):  
Laila Samady ◽  
Emanuela Costigliola ◽  
Luci MacCormac ◽  
Yvonne McGrath ◽  
Steve Cleverley ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Dendritic Cell ◽  
Cell Activation ◽  
Dendritic Cell Activation ◽  
Virus Growth ◽  
Virion Host Shutoff ◽  
Virion Host Shutoff Protein ◽  
Host Shutoff ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) infects dendritic cells (DC) efficiently but with minimal replication. HSV, therefore, appears to have evolved the ability to enter DC even though they are nonpermissive for virus growth. This provides a potential utility for HSV in delivering genes to DC for vaccination purposes and also suggests that the life cycle of HSV usually includes the infection of DC. However, DC infected with HSV usually lose the ability to become activated following infection (M. Salio, M. Cella, M. Suter, and A. Lanzavecchia, Eur. J. Immunol. 29:3245-3253, 1999; M. Kruse, O. Rosorius, F. Kratzer, G. Stelz, C. Kuhnt, G. Schuler, J. Hauber, and A. Steinkasserer, J. Virol. 74:7127-7136, 2000). We report that for DC to retain the ability to become activated following HSV infection, the virion host shutoff protein (vhs) must be deleted. vhs usually functions to destabilize mRNA in favor of the production of HSV proteins in permissive cells. We have found that it also plays a key role in the inactivation of DC and is therefore likely to be important for immune evasion by the virus. Here, vhs would be anticipated to prevent DC activation in the early stages of infection of an individual with HSV, reducing the induction of cellular immune responses and thus preventing virus clearance during repeated cycles of virus latency and reactivation. Based on this information, replication-incompetent HSV vectors with vhs deleted which allow activation of DC and the induction of specific T-cell responses to delivered antigens have been constructed. These responses are greater than if DC are loaded with antigen by incubation with recombinant protein.

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