Recognition of Herpes Simplex Viruses: Toll-like Receptors and Beyond

Overview

Journal J Mol Biol

Publisher Elsevier

Specialties Microbiology
Molecular Biology

Date 2013 Nov 23

PMID 24262390

Citations 59

Authors

Yijie Ma

Bin He

Affiliations

Soon will be listed here.

Abstract

Herpes simplex viruses (HSVs) are human pathogens that establish lytic and latent infections. Reactivation from latency occurs intermittently, which represents a lifelong source of recurrent infection. In this complex process, HSV triggers and neutralizes innate immunity. Therefore, a dynamic equilibrium between HSV and the innate immune system determines the outcome of viral infection. Detection of HSV involves pathogen recognition receptors that include Toll-like receptors, retinoic acid-inducible gene I-like receptors, and cytosolic DNA sensors. Moreover, innate components or pathways exist to sense membrane fusion upon viral entry into host cells. Consequently, this surveillance network activates downstream transcription factors, leading to the induction of type I interferon and inflammatory cytokines. Not surprisingly, with the capacity to establish chronic infection HSV has evolved strategies that modulate or evade innate immunity. In this review, we describe recent advances pertinent to the interplay of HSV and the induction of innate immunity mediated by pathogen recognition receptors or pathways.

Citing Articles

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References

Takeda K, Akira S . TLR signaling pathways. Semin Immunol. 2004; 16(1):3-9. DOI: 10.1016/j.smim.2003.10.003. View

Conrady C, Zheng M, Fitzgerald K, Liu C, Carr D . Resistance to HSV-1 infection in the epithelium resides with the novel innate sensor, IFI-16. Mucosal Immunol. 2012; 5(2):173-83. PMC: 3288395. DOI: 10.1038/mi.2011.63. View

Kim J, Lee S, Kim S, Kim J, Kim H, Lee H . HSV-1 ICP27 suppresses NF-kappaB activity by stabilizing IkappaBalpha. FEBS Lett. 2008; 582(16):2371-6. DOI: 10.1016/j.febslet.2008.05.044. View

Sun W, Li Y, Chen L, Chen H, You F, Zhou X . ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. Proc Natl Acad Sci U S A. 2009; 106(21):8653-8. PMC: 2689030. DOI: 10.1073/pnas.0900850106. View

He B, Gross M, Roizman B . The gamma134.5 protein of herpes simplex virus 1 has the structural and functional attributes of a protein phosphatase 1 regulatory subunit and is present in a high molecular weight complex with the enzyme in infected cells. J Biol Chem. 1998; 273(33):20737-43. DOI: 10.1074/jbc.273.33.20737. View

Cotter C, Kim W, Nguyen M, Yount J, Lopez C, Blaho J . The virion host shutoff protein of herpes simplex virus 1 blocks the replication-independent activation of NF-κB in dendritic cells in the absence of type I interferon signaling. J Virol. 2011; 85(23):12662-72. PMC: 3209407. DOI: 10.1128/JVI.05557-11. View

Piroozmand A, Koyama A, Shimada Y, Fujita M, Arakawa T, Adachi A . Role of Us3 gene of herpes simplex virus type 1 for resistance to interferon. Int J Mol Med. 2004; 14(4):641-5. View

Peri P, Mattila R, Kantola H, Broberg E, Karttunen H, Waris M . Herpes simplex virus type 1 Us3 gene deletion influences toll-like receptor responses in cultured monocytic cells. Virol J. 2008; 5:140. PMC: 2605447. DOI: 10.1186/1743-422X-5-140. View

Ferguson B, Mansur D, Peters N, Ren H, Smith G . DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. Elife. 2012; 1:e00047. PMC: 3524801. DOI: 10.7554/eLife.00047. View

10.

Leib D, Machalek M, Williams B, Silverman R, Virgin H . Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene. Proc Natl Acad Sci U S A. 2000; 97(11):6097-101. PMC: 18564. DOI: 10.1073/pnas.100415697. View

11.

Cotter C, Nguyen M, Yount J, Lopez C, Blaho J, Moran T . The virion host shut-off (vhs) protein blocks a TLR-independent pathway of herpes simplex virus type 1 recognition in human and mouse dendritic cells. PLoS One. 2010; 5(2):e8684. PMC: 2823768. DOI: 10.1371/journal.pone.0008684. View

12.

Paladino P, Mossman K . Mechanisms employed by herpes simplex virus 1 to inhibit the interferon response. J Interferon Cytokine Res. 2009; 29(9):599-607. DOI: 10.1089/jir.2009.0074. View

13.

Daubeuf S, Singh D, Tan Y, Liu H, Federoff H, Bowers W . HSV ICP0 recruits USP7 to modulate TLR-mediated innate response. Blood. 2008; 113(14):3264-75. PMC: 3401030. DOI: 10.1182/blood-2008-07-168203. View

14.

Paladino P, Collins S, Mossman K . Cellular localization of the herpes simplex virus ICP0 protein dictates its ability to block IRF3-mediated innate immune responses. PLoS One. 2010; 5(4):e10428. PMC: 2861674. DOI: 10.1371/journal.pone.0010428. View

15.

Soulat D, Burckstummer T, Westermayer S, Goncalves A, Bauch A, Stefanovic A . The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J. 2008; 27(15):2135-46. PMC: 2453059. DOI: 10.1038/emboj.2008.126. View

16.

Cassady K, Gross M, Gillespie G, Roizman B . Second-site mutation outside of the U(S)10-12 domain of Deltagamma(1)34.5 herpes simplex virus 1 recombinant blocks the shutoff of protein synthesis induced by activated protein kinase R and partially restores neurovirulence. J Virol. 2002; 76(3):942-9. PMC: 135782. DOI: 10.1128/jvi.76.3.942-949.2002. View

17.

Pasieka T, Lu B, Crosby S, Wylie K, Morrison L, Alexander D . Herpes simplex virus virion host shutoff attenuates establishment of the antiviral state. J Virol. 2008; 82(11):5527-35. PMC: 2395185. DOI: 10.1128/JVI.02047-07. View

18.

Collins S, Noyce R, Mossman K . Innate cellular response to virus particle entry requires IRF3 but not virus replication. J Virol. 2004; 78(4):1706-17. PMC: 369475. DOI: 10.1128/jvi.78.4.1706-1717.2004. View

19.

Zhong B, Yang Y, Li S, Wang Y, Li Y, Diao F . The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity. 2008; 29(4):538-50. DOI: 10.1016/j.immuni.2008.09.003. View

20.

Unterholzner L, Keating S, Baran M, Horan K, Jensen S, Sharma S . IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol. 2010; 11(11):997-1004. PMC: 3142795. DOI: 10.1038/ni.1932. View