Herpes Simplex Virus Type 1 DNA Polymerase Requires the Mammalian Chaperone Hsp90 for Proper Localization to the Nucleus

Burch, April D.; Weller, Sandra K.

doi:10.1128/jvi.79.16.10740-10749.2005

Cited by 130 publications

(155 citation statements)

References 30 publications

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“…As previously described, HSV-1 infection results in the redistribution of Hsc70 from the nucleolus into VICE domains located adjacent to replication compartments ( Fig. 3C,G) (Burch and Weller, 2004;Burch and Weller, 2005). A subset of P-RPA foci also colocalized with the Hsc70-staining VICE domains ( Fig.…”

Section: Resultsmentioning

confidence: 59%

“…This sequestration may prevent cellular events, such as premature apoptosis, which would be catastrophic to the virus (Burch and Weller, 2004). The P-RPA staining pattern observed during infection exhibited a nuclear organization reminiscent of that observed for VICE domains (Burch and Weller, 2004;Burch and Weller, 2005;Everett, 2000). To confirm this, we examined cells that were triple-labeled with antibodies to UL29, Hsc70 (Heat shock cognate 70) and P-RPA to visualize replication compartments, VICE domains and endogenous P-RPA, respectively (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Connell et al, 2001;Demand et al, 2001;Doong et al, 2003). The redistribution of Hsc70, Hsp70, Hsp40, Hsp90, ubiquitylated proteins and the core catalytic complex of the proteasome into VICE domains in infected cells suggests that HSV-1 has evolved a mechanism to deal with misfolded and unwanted proteins (Burch and Weller, 2004;Burch and Weller, 2005;Parkinson and Everett, 2001). VICE domains are reminiscent of nuclear aggresomes, which form in response to misfolded proteins and contain heat-shock proteins and components of the ubiquitin proteasome (Anton et al, 1999;Fu et al, 2005).…”

Section: Vice Domains and Sequestration Of Non-native Proteinsmentioning

confidence: 99%

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Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection

Wilkinson

Weller

2006

Journal of Cell Science

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Like other DNA viruses, herpes simplex virus type 1 (HSV-1) interacts with components of the cellular response to DNA damage. For example, HSV-1 sequesters endogenous, uninduced, hyperphosphorylated RPA (replication protein A) away from viral replication compartments. RPA is a ssDNA-binding protein that signals genotoxic stress through the ATR (ataxia telangiectasia-mutated and Rad3-related) pathway. The sequestration of endogenous hyperphosphorylated RPA away from replicating viral DNA suggests that HSV-1 prevents the normal ATRsignaling response. In this study we examine the spatial distribution of endogenous hyperphosphorylated RPA with respect to ATR, its recruitment factor, ATRIP, and the cellular dsDNA break marker, ␥ ␥H2AX, during HSV-1 infection. The accumulation of these repair factors at DNA lesions has previously been identified as an early event in signaling genotoxic stress. We show that HSV-1 infection disrupts the ATR pathway by a mechanism that prevents the recruitment of repair factors, spatially uncouples ATRIP from ATR and sequesters ATRIP and endogenous hyperphosphorylated RPA within virus-induced nuclear domains containing molecular chaperones and components of the ubiquitin proteasome. The HSV-1 immediate early protein ICP0 is sufficient to induce the redistribution of ATRIP. This is the first report that a virus can disrupt the usually tight colocalization of ATR and ATRIP.

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Section: Resultsmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Vice Domains and Sequestration Of Non-native Proteinsmentioning

confidence: 99%

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Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection

Wilkinson

Weller

2006

Journal of Cell Science

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“…In addition, the HSP90 trafficking complex has been shown to mediate the import of numerous cellular and viral proteins to the nucleus, playing a critical role in the replication and growth of several viruses. For example, herpes simplex virus type 1 DNA polymerase requires HSP90 for proper localization to the nucleus (Burch & Weller, 2005); it also acts as a stimulatory host factor involved in influenza virus RNA synthesis (Momose et al, 2002). Another study demonstrated that HSP90 is important for vaccinia virus growth in cultured cells through interaction with viral core protein 4a (Hung et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Role of heat-shock protein 90 in hepatitis E virus capsid trafficking

Zheng

Jiang

Zhao

et al. 2010

Journal of General Virology

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p239 is a virus-like particle constituted from hepatitis E virus (HEV) recombinant proteins. It can be used as a surrogate for HEV and as an investigative tool to study cellular interactions because of its ability to adsorb to and penetrate HepG2 cellular membranes. Our objective was to use p239 to define the role of HEV capsid proteins during the early stages of infection. Pull-down and MALDI-TOF MS experiments identified three host-cell proteins, Grp 78/Bip, a-tubulin and heatshock protein 90 (HSP90), and the latter was investigated further. Antibodies to p239 alone or HSP90 alone could detect p239 or HSP90, suggesting the formation of a complex between p239 and HSP90. In the HepG2 cell, geldanamycin (GA), an HSP90-specific inhibitor, blocked intracellular transportation of p239, but had no effect on the binding and cellular entry of p239, suggesting that HSP90 was important for HEV capsid intracellular transportation. RT-PCR results showed that the efficiency of wild-type HEV infection was inhibited significantly by GA treatment, suggesting the importance of HSP90 in virus infectivity. It was concluded that HSP90 plays a crucial role in the intracellular transportation of viral capsids in the early stage of HEV infection.

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“…Probably the closest analogy exists to telomerase, the cellular reverse transcriptase that maintains chromosome end integrity [138,139] . However, also the DNA polymerase of Herpes simplex virus [140] , and the RNA polymerases of flock house virus [141] and influenza virus appear to require chaperone assistance [142,143] . Closely watching progress in those areas might also provide clues as to the mechanism of chaperone-assisted hepadnavirus replication; however, for polymerases without a similarly sophisticated protein-primed initiation mode the chaperones could act at rather different levels.…”

Section: Importance Of Chaperones For Hepadnavirus Replication In Intmentioning

confidence: 99%

Hepatitis B virus replication

Beck

Nassal

2007

WJG

413

382

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Hepadnaviruses, including human hepatitis B virus (HBV), replicate through reverse transcription of an RNA intermediate, the pregenomic RNA (pgRNA). Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription: it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA, ε, as template, and depends on cellular chaperones; moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids. This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV (DHBV), now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cellfree systems. At this time, they can, unfortunately, not be complemented by three-dimensional structural information on the involved components. However, at least for the ε RNA element such information is emerging, raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal, will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.© 2007 The WJG Press. All rights reserved. Dieter Glebe, PhD, Series EditorPO Box 2345, Beijing 100023, China World J Gastroenterol 2007 January 7; 13(1): 48-64 www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327 wjg@wjgnet.com © 2007 OVERVIEW OVER THE HEPADNAVIRAL GENOME REPLICATION CYCLEReplication of the hepadnaviral genome can broadly be divided into three phases ( Figure 1): (1) Infectious virions contain in their inner icosahedral core the genome as a partially double-stranded, circular but not covalently closed DNA of about 3.2 kb in length (relaxed circular, or RC-DNA); (2) upon infection, the RC-DNA is converted, inside the host cell nucleus, into a plasmid-like covalently closed circular DNA (cccDNA); (3) from the cccDNA, several genomic and subgenomic RNAs are transcribed by cellular RNA polymerase Ⅱ; of these, the pregenomic RNA (pgRNA) is selectively packaged into progeny capsids and is reverse transcribed by the co-packaged P protein into new RC-DNA genomes. Matured RC-DNA containing-but not immature RNA containingnucleocapsids can be used for intracellular cccDNA amplification, or be enveloped and released from the cell as progeny virions. Below we discuss these genome conversions, with emphasis on the reverse transcription step, and particularly its unique initiation mechanism. RC-DNA TO cccDNA CONVERSIONPersistent viral infections require tha...

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Herpes Simplex Virus Type 1 DNA Polymerase Requires the Mammalian Chaperone Hsp90 for Proper Localization to the Nucleus

Cited by 130 publications

References 30 publications

Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection

Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection

Role of heat-shock protein 90 in hepatitis E virus capsid trafficking

Hepatitis B virus replication

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