Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 317 (5844): 1522-1527

Copyright © 2007 by the American Association for the Advancement of Science

TLR3 Deficiency in Patients with Herpes Simplex Encephalitis

Shen-Ying Zhang,123 Emmanuelle Jouanguy,123 Sophie Ugolini,4 Asma Smahi,5 Gaëlle Elain,6 Pedro Romero,7 David Segal,8 Vanessa Sancho-Shimizu,12 Lazaro Lorenzo,12 Anne Puel,12 Capucine Picard,129 Ariane Chapgier,12 Sabine Plancoulaine,12 Matthias Titeux,10 Céline Cognet,4 Horst von Bernuth,12 Cheng-Lung Ku,12 Armanda Casrouge,12 Xin-Xin Zhang,3 Luis Barreiro,11 Joshua Leonard,8 Claire Hamilton,12 Pierre Lebon,12 Bénédicte Héron,13 Louis Vallée,14 Lluis Quintana-Murci,11 Alain Hovnanian,10 Flore Rozenberg,12 Eric Vivier,4 Frédéric Geissmann,6 Marc Tardieu,15 Laurent Abel,12 Jean-Laurent Casanova12316*

Abstract: Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3-independent pathways to prevent further dissemination of HSV-1 and to provide resistance to other pathogens in TLR3-deficient patients. Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3.

1 Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), U550, Faculty Necker, Paris 75015, France.
2 University Paris René Descartes, Paris 75015, France.
3 French-Chinese Laboratory of Genetics and Life Sciences, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
4 Marseille-Luminy Immunology Institute, Marseille 13288, France.
5 Department of Genetics, INSERM, U781, Necker Hospital, Paris 75015, France.
6 Laboratory of Mononuclear Cell Biology, INSERM, U838, Necker Hospital, Paris 75015, France.
7 Ludwig Institute for Cancer Research, Lausanne Branch, University Hospital, Lausanne 1005, Switzerland.
8 Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
9 Center for the Study of Immunodeficiencies, Necker Hospital, Paris 75015, France.
10 INSERM, U563, University Toulouse Paul Sabatier, Toulouse 31000, France.
11 Centre National de la Recherche Scientifique, URA3012, Pasteur Institute, Paris 75015, France.
12 Virology, Cochin-Saint-Vincent de Paul Hospital, University Paris René Descartes, Paris 75014, France.
13 Pediatric Neurology, Trousseau Hospital, Paris 75012, France.
14 Pediatric Neurology, University Hospital, Lille 59037, France.
15 Pediatric Neurology, Bicêtre Hospital, University Paris Sud, Kremlin-Bicêtre 94270, France.
16 Pediatric Hematology-Immunology, Necker Hospital, Paris 75015, France.

* To whom correspondence should be addressed. E-mail: casanova{at}necker.fr

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Both TRIF and IPS-1 Adaptor Proteins Contribute to the Cerebral Innate Immune Response against Herpes Simplex Virus 1 Infection.
R. Menasria, N. Boivin, M. Lebel, J. Piret, J. Gosselin, and G. Boivin (2013)
J. Virol. 87, 7301-7308
   Abstract »    Full Text »    PDF »
NK Cells in Central Nervous System Disorders.
A. Poli, J. Kmiecik, O. Domingues, F. Hentges, M. Blery, M. Chekenya, J. Boucraut, and J. Zimmer (2013)
J. Immunol. 190, 5355-5362
   Abstract »    Full Text »    PDF »
The human gene connectome as a map of short cuts for morbid allele discovery.
Y. Itan, S.-Y. Zhang, G. Vogt, A. Abhyankar, M. Herman, P. Nitschke, D. Fried, L. Quintana-Murci, L. Abel, and J.-L. Casanova (2013)
PNAS 110, 5558-5563
   Abstract »    Full Text »    PDF »
Recognition of pathogen-associated nucleic acids by endosomal nucleic acid-sensing toll-like receptors.
X. He, H. Jia, Z. Jing, and D. Liu (2013)
Acta Biochim Biophys Sin 45, 241-258
   Abstract »    Full Text »    PDF »
Microglia and a Functional Type I IFN Pathway Are Required To Counter HSV-1-Driven Brain Lateral Ventricle Enlargement and Encephalitis.
C. D. Conrady, M. Zheng, N. van Rooijen, D. A. Drevets, D. Royer, A. Alleman, and D. J. J. Carr (2013)
J. Immunol. 190, 2807-2817
   Abstract »    Full Text »    PDF »
Proteasomal Degradation of Herpes Simplex Virus Capsids in Macrophages Releases DNA to the Cytosol for Recognition by DNA Sensors.
K. A. Horan, K. Hansen, M. R. Jakobsen, C. K. Holm, S. Soby, L. Unterholzner, M. Thompson, J. A. West, M. B. Iversen, S. B. Rasmussen, et al. (2013)
J. Immunol. 190, 2311-2319
   Abstract »    Full Text »    PDF »
STAT2 deficiency and susceptibility to viral illness in humans.
S. Hambleton, S. Goodbourn, D. F. Young, P. Dickinson, S. M. B. Mohamad, M. Valappil, N. McGovern, A. J. Cant, S. J. Hackett, P. Ghazal, et al. (2013)
PNAS 110, 3053-3058
   Abstract »    Full Text »    PDF »
Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus.
F. Qian, C. R. Bolen, C. Jing, X. Wang, W. Zheng, H. Zhao, E. Fikrig, R. D. Bruce, S. H. Kleinstein, and R. R. Montgomery (2013)
Clin. Vaccine Immunol. 20, 146-155
   Abstract »    Full Text »    PDF »
Neurotropic Arboviruses Induce Interferon Regulatory Factor 3-Mediated Neuronal Responses That Are Cytoprotective, Interferon Independent, and Inhibited by Western Equine Encephalitis Virus Capsid.
D. C. Peltier, H. M. Lazear, J. R. Farmer, M. S. Diamond, and D. J. Miller (2013)
J. Virol. 87, 1821-1833
   Abstract »    Full Text »    PDF »
Natural Killer Cell Functional Defects in Pediatric Patients With Severe and Recurrent Herpesvirus Infections.
B. W. Ornstein, E. B. Hill, T. L. Geurs, and A. R. French (2013)
The Journal of Infectious Disease 207, 458-468
   Abstract »    Full Text »    PDF »
Potential Function of miRNAs in Herpetic Stromal Keratitis.
S. Mulik, S. Bhela, and B. T. Rouse (2013)
Invest. Ophthalmol. Vis. Sci. 54, 563-573
   Abstract »    Full Text »    PDF »
Broad RNA Interference-Mediated Antiviral Immunity and Virus-Specific Inducible Responses in Drosophila.
C. Kemp, S. Mueller, A. Goto, V. Barbier, S. Paro, F. Bonnay, C. Dostert, L. Troxler, C. Hetru, C. Meignin, et al. (2013)
J. Immunol. 190, 650-658
   Abstract »    Full Text »    PDF »
Cleaved/Associated TLR3 Represents the Primary Form of the Signaling Receptor.
F. Toscano, Y. Estornes, F. Virard, A. Garcia-Cattaneo, A. Pierrot, B. Vanbervliet, M. Bonnin, M. J. Ciancanelli, S.-Y. Zhang, K. Funami, et al. (2013)
J. Immunol. 190, 764-773
   Abstract »    Full Text »    PDF »
IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4-, MyD88-, and TIRAP- but not UNC-93B-deficient patients.
S. Weller, M. Bonnet, H. Delagreverie, L. Israel, M. Chrabieh, L. Marodi, C. Rodriguez-Gallego, B.-Z. Garty, C. Roifman, A. C. Issekutz, et al. (2012)
Blood 120, 4992-5001
   Abstract »    Full Text »    PDF »
Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised.
I. L. Tan, J. C. McArthur, A. Venkatesan, and A. Nath (2012)
Neurology 79, 2125-2132
   Abstract »    Full Text »    PDF »
Peripheral Blood CD4 T-Cell and Plasmacytoid Dendritic Cell (pDC) Reactivity to Herpes Simplex Virus 2 and pDC Number Do Not Correlate with the Clinical or Virologic Severity of Recurrent Genital Herpes.
N. J. Moss, A. Magaret, K. J. Laing, A. S. Kask, M. Wang, K. E. Mark, J. T. Schiffer, A. Wald, and D. M. Koelle (2012)
J. Virol. 86, 9952-9963
   Abstract »    Full Text »    PDF »
Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood.
M. Herman, M. Ciancanelli, Y.-H. Ou, L. Lorenzo, M. Klaudel-Dreszler, E. Pauwels, V. Sancho-Shimizu, R. Perez de Diego, A. Abhyankar, E. Israelsson, et al. (2012)
J. Exp. Med. 209, 1567-1582
   Abstract »    Full Text »    PDF »
Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection.
A. Svensson, P. Tunback, I. Nordstrom, L. Padyukov, and K. Eriksson (2012)
J. Gen. Virol. 93, 1717-1724
   Abstract »    Full Text »    PDF »
Extracellularly Delivered Single-Stranded Viral RNA Causes Neurodegeneration Dependent on TLR7.
S. M. Lehmann, K. Rosenberger, C. Kruger, P. Habbel, K. Derkow, D. Kaul, A. Rybak, C. Brandt, E. Schott, F. G. Wulczyn, et al. (2012)
J. Immunol. 189, 1448-1458
   Abstract »    Full Text »    PDF »
Heterozygous Carriage of a Dysfunctional Toll-like Receptor 9 Allele Affects CpG Oligonucleotide Responses in B Cells.
J. Knezevic, D. Pavlinic, W. A. Rose II, C. A. Leifer, K. Bendelja, J. Gabrilovac, M. Parcina, G. Lauc, A. V. Kubarenko, B. Petricevic, et al. (2012)
J. Biol. Chem. 287, 24544-24553
   Abstract »    Full Text »    PDF »
Herpes Simplex Virus Glycoproteins gH/gL and gB Bind Toll-Like Receptor 2, and Soluble gH/gL Is Sufficient To Activate NF-{kappa}B.
V. Leoni, T. Gianni, S. Salvioli, and G. Campadelli-Fiume (2012)
J. Virol. 86, 6555-6562
   Abstract »    Full Text »    PDF »
Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling.
A. Garcia-Cattaneo, F.-X. Gobert, M. Muller, F. Toscano, M. Flores, A. Lescure, E. Del Nery, and P. Benaroch (2012)
PNAS 109, 9053-9058
   Abstract »    Full Text »    PDF »
Herpes encephalitis during natalizumab treatment in multiple sclerosis.
A. Kwiatkowski, J. Gallois, N. Bilbault, G. Calais, A. Mackowiak, and P. Hautecoeur (2012)
Multiple Sclerosis Journal 18, 909-911
   Abstract »    Full Text »    PDF »
Host Genetic Factors in Susceptibility to Herpes Simplex Type 1 Virus Infection: Contribution of Polymorphic Genes at the Interface of Innate and Adaptive Immunity.
M. Moraru, E. Cisneros, N. Gomez-Lozano, R. de Pablo, F. Portero, M. Canizares, M. Vaquero, G. Roustan, I. Millan, M. Lopez-Botet, et al. (2012)
J. Immunol. 188, 4412-4420
   Abstract »    Full Text »    PDF »
A TRIF-Independent Branch of TLR3 Signaling.
M. Yamashita, S. Chattopadhyay, V. Fensterl, Y. Zhang, and G. C. Sen (2012)
J. Immunol. 188, 2825-2833
   Abstract »    Full Text »    PDF »
Role of Specific Innate Immune Responses in Herpes Simplex Virus Infection of the Central Nervous System.
J. P. Wang, G. N. Bowen, S. Zhou, A. Cerny, A. Zacharia, D. M. Knipe, R. W. Finberg, and E. A. Kurt-Jones (2012)
J. Virol. 86, 2273-2281
   Abstract »    Full Text »    PDF »
Inhibition of TANK Binding Kinase 1 by Herpes Simplex Virus 1 Facilitates Productive Infection.
Y. Ma, H. Jin, T. Valyi-Nagy, Y. Cao, Z. Yan, and B. He (2012)
J. Virol. 86, 2188-2196
   Abstract »    Full Text »    PDF »
TLR3 essentially promotes protective class I-restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients.
A. Carvalho, A. De Luca, S. Bozza, C. Cunha, C. D'Angelo, S. Moretti, K. Perruccio, R. G. Iannitti, F. Fallarino, A. Pierini, et al. (2012)
Blood 119, 967-977
   Abstract »    Full Text »    PDF »
Activation of NF-{kappa}B in CD8+ Dendritic Cells Ex Vivo by the {gamma}134.5 Null Mutant Correlates with Immunity against Herpes Simplex Virus 1.
H. Jin, Y. Ma, Z. Yan, B. S. Prabhakar, and B. He (2012)
J. Virol. 86, 1059-1068
   Abstract »    Full Text »    PDF »
A Common Polymorphism in TLR3 Confers Natural Resistance to HIV-1 Infection.
M. Sironi, M. Biasin, R. Cagliani, D. Forni, M. De Luca, I. Saulle, S. Lo Caputo, F. Mazzotta, J. Macias, J. A. Pineda, et al. (2012)
J. Immunol. 188, 818-823
   Abstract »    Full Text »    PDF »
Multiplex Sequencing of Seven Ocular Herpes Simplex Virus Type-1 Genomes: Phylogeny, Sequence Variability, and SNP Distribution.
A. W. Kolb, M. Adams, E. L. Cabot, M. Craven, and C. R. Brandt (2011)
Invest. Ophthalmol. Vis. Sci. 52, 9061-9073
   Abstract »    Full Text »    PDF »
The TLR3/TICAM-1 Pathway Is Mandatory for Innate Immune Responses to Poliovirus Infection.
H. Oshiumi, M. Okamoto, K. Fujii, T. Kawanishi, M. Matsumoto, S. Koike, and T. Seya (2011)
J. Immunol. 187, 5320-5327
   Abstract »    Full Text »    PDF »
Severe Viral Infections and Primary Immunodeficiencies.
L. K. Dropulic and J. I. Cohen (2011)
Clinical Infectious Diseases 53, 897-909
   Abstract »    Full Text »    PDF »
TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes.
M. Swiecki, S. A. McCartney, Y. Wang, and M. Colonna (2011)
J. Leukoc. Biol. 90, 691-701
   Abstract »    Full Text »    PDF »
Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity.
Y. Guo, M. Audry, M. Ciancanelli, L. Alsina, J. Azevedo, M. Herman, E. Anguiano, V. Sancho-Shimizu, L. Lorenzo, E. Pauwels, et al. (2011)
J. Exp. Med. 208, 2083-2098
   Abstract »    Full Text »    PDF »
H5N1 Influenza Virus Pathogenesis in Genetically Diverse Mice Is Mediated at the Level of Viral Load.
A. C. M. Boon, D. Finkelstein, M. Zheng, G. Liao, J. Allard, K. Klumpp, R. Webster, G. Peltz, and R. J. Webby (2011)
mBio 2, e00171-11
   Abstract »    Full Text »    PDF »
Herpes simplex virus type 2 virion host shutoff protein suppresses innate dsRNA antiviral pathways in human vaginal epithelial cells.
X.-D. Yao and K. L. Rosenthal (2011)
J. Gen. Virol. 92, 1981-1993
   Abstract »    Full Text »    PDF »
Evolution of the TIR Domain-Containing Adaptors in Humans: Swinging between Constraint and Adaptation.
S. Fornarino, G. Laval, L. B. Barreiro, J. Manry, E. Vasseur, and L. Quintana-Murci (2011)
Mol. Biol. Evol.
   Abstract »    Full Text »    PDF »
Microbial Sensing by Toll Receptors: A Historical Perspective.
S. Chtarbanova and J.-L. Imler (2011)
Arterioscler Thromb Vasc Biol 31, 1734-1738
   Abstract »    Full Text »    PDF »
Infectious Diseases in Patients with IRAK-4, MyD88, NEMO, or I{kappa}B{alpha} Deficiency.
C. Picard, J.-L. Casanova, and A. Puel (2011)
Clin. Microbiol. Rev. 24, 490-497
   Abstract »    Full Text »    PDF »
Sequence Variation in the Herpes Simplex Virus US1 Ocular Virulence Determinant.
A. W. Kolb, T. R. Schmidt, D. W. Dyer, and C. R. Brandt (2011)
Invest. Ophthalmol. Vis. Sci. 52, 4630-4638
   Abstract »    Full Text »    PDF »
Impaired Interferon Signaling in Dendritic Cells From Older Donors Infected In Vitro With West Nile Virus.
F. Qian, X. Wang, L. Zhang, A. Lin, H. Zhao, E. Fikrig, and R. R. Montgomery (2011)
The Journal of Infectious Disease 203, 1415-1424
   Abstract »    Full Text »    PDF »
Toll-like Receptor 3 (TLR3) Induces Apoptosis via Death Receptors and Mitochondria by Up-regulating the Transactivating p63 Isoform {alpha} (TAP63{alpha}).
R. Sun, Y. Zhang, Q. Lv, B. Liu, M. Jin, W. Zhang, Q. He, M. Deng, X. Liu, G. Li, et al. (2011)
J. Biol. Chem. 286, 15918-15928
   Abstract »    Full Text »    PDF »
Increased Cell-Mediated Immune Responses in Patients with Recurrent Herpes Simplex Virus Type 2 Meningitis.
E. Franzen-Rohl, D. Schepis, M. Lagrelius, K. Franck, P. Jones, J.-A. Liljeqvist, T. Bergstrom, E. Aurelius, K. Karre, L. Berg, et al. (2011)
Clin. Vaccine Immunol. 18, 655-660
   Abstract »    Full Text »    PDF »
TBK1-associated Protein in Endolysosomes (TAPE) Is an Innate Immune Regulator Modulating the TLR3 and TLR4 Signaling Pathways.
C.-H. Chang, L.-C. Lai, H.-C. Cheng, K.-R. Chen, Y.-Z. Syue, H.-C. Lu, W.-Y. Lin, S.-H. Chen, H.-S. Huang, A.-L. Shiau, et al. (2011)
J. Biol. Chem. 286, 7043-7051
   Abstract »    Full Text »    PDF »
Early ''Relapse'' After Herpetic Encephalitis: Extensive White Matter Lesions in an Infant With Interferon Production Deficit.
R. Maia, C. Gouveia, A. Moreira, J. L. Casanova, V. Sancho-Shimizu, and M. J. Brito (2011)
J Child Neurol 26, 369-372
   Abstract »    PDF »
A Functional Toll-Like Receptor 3 Gene (TLR3) May Be a Risk Factor for Tick-borne Encephalitis Virus (TBEV) Infection.
E. Kindberg, S. Vene, A. Mickiene, A. Lundkvist, L. Lindquist, and L. Svensson (2011)
The Journal of Infectious Disease 203, 523-528
   Abstract »    Full Text »    PDF »
EBV Lytic-Phase Protein BGLF5 Contributes to TLR9 Downregulation during Productive Infection.
M. van Gent, B. D. Griffin, E. G. Berkhoff, D. van Leeuwen, I. G. J. Boer, M. Buisson, F. C. Hartgers, W. P. Burmeister, E. J. Wiertz, and M. E. Ressing (2011)
J. Immunol. 186, 1694-1702
   Abstract »    Full Text »    PDF »
Two Human MYD88 Variants, S34Y and R98C, Interfere with MyD88-IRAK4-Myddosome Assembly.
J. George, P. G. Motshwene, H. Wang, A. V. Kubarenko, A. Rautanen, T. C. Mills, A. V. S. Hill, N. J. Gay, and A. N. R. Weber (2011)
J. Biol. Chem. 286, 1341-1353
   Abstract »    Full Text »    PDF »
A Naturally Occurring Variant in Human TLR9, P99L, Is Associated with Loss of CpG Oligonucleotide Responsiveness.
A. V. Kubarenko, S. Ranjan, A. Rautanen, T. C. Mills, S. Wong, F. Vannberg, M. Neumaier, I. Bekeredjian-Ding, A. V. S. Hill, P. Ahmad-Nejad, et al. (2010)
J. Biol. Chem. 285, 36486-36494
   Abstract »    Full Text »    PDF »
Secretion of the Human Toll-like Receptor 3 Ectodomain Is Affected by Single Nucleotide Polymorphisms and Regulated by Unc93b1.
R. Qi, S. Hoose, J. Schreiter, K. V. Sawant, R. Lamb, C. T. Ranjith-Kumar, J. Mills, L. S. Mateo, J. L. Jordan, and C. C. Kao (2010)
J. Biol. Chem. 285, 36635-36644
   Abstract »    Full Text »    PDF »
Early Innate Recognition of Herpes Simplex Virus in Human Primary Macrophages Is Mediated via the MDA5/MAVS-Dependent and MDA5/MAVS/RNA Polymerase III-Independent Pathways.
J. Melchjorsen, J. Rintahaka, S. Soby, K. A. Horan, A. Poltajainen, L. Ostergaard, S. R. Paludan, and S. Matikainen (2010)
J. Virol. 84, 11350-11358
   Abstract »    Full Text »    PDF »
Interferon Regulatory Factor 3-Dependent Pathways Are Critical for Control of Herpes Simplex Virus Type 1 Central Nervous System Infection.
V. D. Menachery, T. J. Pasieka, and D. A. Leib (2010)
J. Virol. 84, 9685-9694
   Abstract »    Full Text »    PDF »
A Role for Toll-like Receptor 3 Variants in Host Susceptibility to Enteroviral Myocarditis and Dilated Cardiomyopathy.
C. Gorbea, K. A. Makar, M. Pauschinger, G. Pratt, J. L. F. Bersola, J. Varela, R. M. David, L. Banks, C.-H. Huang, H. Li, et al. (2010)
J. Biol. Chem. 285, 23208-23223
   Abstract »    Full Text »    PDF »
Viral Infection of the Placenta Leads to Fetal Inflammation and Sensitization to Bacterial Products Predisposing to Preterm Labor.
I. Cardenas, R. E. Means, P. Aldo, K. Koga, S. M. Lang, C. Booth, A. Manzur, E. Oyarzun, R. Romero, and G. Mor (2010)
J. Immunol. 185, 1248-1257
   Abstract »    Full Text »    PDF »
Identification of an Important Immunological Difference between Virulent Varicella-Zoster Virus and Its Avirulent Vaccine: Viral Disruption of Dendritic Cell Instruction.
C. Gutzeit, M. J. Raftery, M. Peiser, K. B. Tischer, M. Ulrich, M. Eberhardt, E. Stockfleth, T. Giese, A. Sauerbrei, C. T. Morita, et al. (2010)
J. Immunol. 185, 488-497
   Abstract »    Full Text »    PDF »
Human Neuronal Cells Possess Functional Cytoplasmic and TLR-Mediated Innate Immune Pathways Influenced by Phosphatidylinositol-3 Kinase Signaling.
D. C. Peltier, A. Simms, J. R. Farmer, and D. J. Miller (2010)
J. Immunol. 184, 7010-7021
   Abstract »    Full Text »    PDF »
Phagocytosis of Enterovirus-Infected Pancreatic {beta}-Cells Triggers Innate Immune Responses in Human Dendritic Cells.
B. M. Schulte, M. Kramer, M. Ansems, K. H. W. Lanke, N. van Doremalen, J. D. Piganelli, R. Bottino, M. Trucco, J. M. D. Galama, G. J. Adema, et al. (2010)
Diabetes 59, 1182-1191
   Abstract »    Full Text »    PDF »
Detailed Characterization of T Cell Responses to Herpes Simplex Virus-2 in Immune Seronegative Persons.
C. M. Posavad, M. Remington, D. E. Mueller, L. Zhao, A. S. Magaret, A. Wald, and L. Corey (2010)
J. Immunol. 184, 3250-3259
   Abstract »    Full Text »    PDF »
Beta interferon plus gamma interferon efficiently reduces acyclovir-resistant herpes simplex virus infection in mice in a T-cell-independent manner.
W.-Y. Huang, Y.-H. Su, H.-W. Yao, P. Ling, Y.-Y. Tung, S.-H. Chen, X. Wang, and S.-H. Chen (2010)
J. Gen. Virol. 91, 591-598
   Abstract »    Full Text »    PDF »
Cutting Edge: Priming of CD8 T Cell Immunity to Herpes Simplex Virus Type 1 Requires Cognate TLR3 Expression In Vivo.
G. M. Davey, M. Wojtasiak, A. I. Proietto, F. R. Carbone, W. R. Heath, and S. Bedoui (2010)
J. Immunol. 184, 2243-2246
   Abstract »    Full Text »    PDF »
VEGF-A expression by HSV-1-infected cells drives corneal lymphangiogenesis.
T. R. Wuest and D. J.J. Carr (2010)
J. Exp. Med. 207, 101-115
   Abstract »    Full Text »    PDF »
Severe Meningoencephalitis Due to Late Reactivation of Varicella-Zoster Virus in an Immunocompetent Child.
R. Spiegel, D. Miron, D. Lumelsky, and Y. Horovitz (2010)
J Child Neurol 25, 87-90
   Abstract »    PDF »
Infectious Encephalitis in France in 2007: A National Prospective Study.
A. Mailles, J.-P. Stahl, and behalf of the Steering Committee and the Investiga (2009)
Clinical Infectious Diseases 49, 1838-1847
   Abstract »    Full Text »    PDF »
Encephalitis: Why We Need to Keep Pushing the Envelope.
C. Glaser and K. C. Bloch (2009)
Clinical Infectious Diseases 49, 1848-1850
   Full Text »    PDF »
Evasion of the Mucosal Innate Immune System by Herpes Simplex Virus Type 2.
T. Peng, J. Zhu, A. Klock, K. Phasouk, M.-L. Huang, D. M. Koelle, A. Wald, and L. Corey (2009)
J. Virol. 83, 12559-12568
   Abstract »    Full Text »    PDF »
Dephosphorylation of eIF2{alpha} Mediated by the {gamma}134.5 Protein of Herpes Simplex Virus 1 Facilitates Viral Neuroinvasion.
D. Verpooten, Z. Feng, T. Valyi-Nagy, Y. Ma, H. Jin, Z. Yan, C. Zhang, Y. Cao, and B. He (2009)
J. Virol. 83, 12626-12630
   Abstract »    Full Text »    PDF »
Control of Herpes Simplex Virus Replication Is Mediated through an Interferon Regulatory Factor 3-Dependent Pathway.
V. D. Menachery and D. A. Leib (2009)
J. Virol. 83, 12399-12406
   Abstract »    Full Text »    PDF »
Host Genetic Variation Affects Resistance to Infection with a Highly Pathogenic H5N1 Influenza A Virus in Mice.
A. C. M. Boon, J. deBeauchamp, A. Hollmann, J. Luke, M. Kotb, S. Rowe, D. Finkelstein, G. Neale, L. Lu, R. W. Williams, et al. (2009)
J. Virol. 83, 10417-10426
   Abstract »    Full Text »    PDF »
Toll-Like Receptor 3 Mediates Establishment of an Antiviral State against Hepatitis C Virus in Hepatoma Cells.
N. Wang, Y. Liang, S. Devaraj, J. Wang, S. M. Lemon, and K. Li (2009)
J. Virol. 83, 9824-9834
   Abstract »    Full Text »    PDF »
Herpes Simplex Encephalitis during Treatment with Tumor Necrosis Factor-{alpha} Inhibitors.
R. D. Bradford, A. C. Pettit, P. W. Wright, M. J. Mulligan, L. W. Moreland, D. A. McLain, J. W. Gnann, and K. C. Bloch (2009)
Clinical Infectious Diseases 49, 924-927
   Abstract »    Full Text »    PDF »
Early Triggering of Exclusive IFN-{gamma} Responses of Human V{gamma}9V{delta}2 T Cells by TLR-Activated Myeloid and Plasmacytoid Dendritic Cells.
M.-C. Devilder, S. Allain, C. Dousset, M. Bonneville, and E. Scotet (2009)
J. Immunol. 183, 3625-3633
   Abstract »    Full Text »    PDF »
Revisiting Crohn's disease as a primary immunodeficiency of macrophages.
J.-L. Casanova and L. Abel (2009)
J. Exp. Med. 206, 1839-1843
   Abstract »    Full Text »    PDF »
Viral Myocarditis: From the Perspective of the Virus.
T. Yajima and K. U. Knowlton (2009)
Circulation 119, 2615-2624
   Full Text »    PDF »
HSV ICP0 recruits USP7 to modulate TLR-mediated innate response.
S. Daubeuf, D. Singh, Y. Tan, H. Liu, H. J. Federoff, W. J. Bowers, and K. Tolba (2009)
Blood 113, 3264-3275
   Abstract »    Full Text »    PDF »
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses.
T. H. Mogensen (2009)
Clin. Microbiol. Rev. 22, 240-273
   Abstract »    Full Text »    PDF »
The roles of TLRs, RLRs and NLRs in pathogen recognition.
T. Kawai and S. Akira (2009)
Int. Immunol. 21, 317-337
   Abstract »    Full Text »    PDF »
Control of TANK-binding Kinase 1-mediated Signaling by the {gamma}134.5 Protein of Herpes Simplex Virus 1.
D. Verpooten, Y. Ma, S. Hou, Z. Yan, and B. He (2009)
J. Biol. Chem. 284, 1097-1105
   Abstract »    Full Text »    PDF »
A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity.
H. Negishi, T. Osawa, K. Ogami, X. Ouyang, S. Sakaguchi, R. Koshiba, H. Yanai, Y. Seko, H. Shitara, K. Bishop, et al. (2008)
PNAS 105, 20446-20451
   Abstract »    Full Text »    PDF »
TLR2 and TLR9 Synergistically Control Herpes Simplex Virus Infection in the Brain.
L. N. Sorensen, L. S. Reinert, L. Malmgaard, C. Bartholdy, A. R. Thomsen, and S. R. Paludan (2008)
J. Immunol. 181, 8604-8612
   Abstract »    Full Text »    PDF »
Myeloid Differentiation Primary Response Gene 88 Is Required for the Resolution of Otitis Media.
M. Hernandez, A. Leichtle, K. Pak, J. Ebmeyer, S. Euteneuer, M. Obonyo, D. G. Guiney, N. J. Webster, D. H. Broide, A. F. Ryan, et al. (2008)
The Journal of Infectious Disease 198, 1862-1869
   Abstract »    Full Text »    PDF »
Toll-Like Receptor 3 Has a Protective Role against West Nile Virus Infection.
S. Daffis, M. A. Samuel, M. S. Suthar, M. Gale Jr., and M. S. Diamond (2008)
J. Virol. 82, 10349-10358
   Abstract »    Full Text »    PDF »
Effect of Pretreatment with Toll-like Receptor Agonists in a Mouse Model of Herpes Simplex Virus Type 1 Encephalitis.
N. Boivin, Y. Sergerie, S. Rivest, and G. Boivin (2008)
The Journal of Infectious Disease 198, 664-672
   Abstract »    Full Text »    PDF »
Prevalence of herpes simplex virus type 1 glycoprotein G (gG) and gI genotypes in patients with herpetic keratitis.
R Duan, J M van Dun, L Remeijer, M Siemerink, P G H Mulder, P Norberg, A D M E Osterhaus, and G M G M Verjans (2008)
Br J Ophthalmol 92, 1195-1200
   Abstract »    Full Text »    PDF »
Pyogenic Bacterial Infections in Humans with MyD88 Deficiency.
H. von Bernuth, C. Picard, Z. Jin, R. Pankla, H. Xiao, C.-L. Ku, M. Chrabieh, I. B. Mustapha, P. Ghandil, Y. Camcioglu, et al. (2008)
Science 321, 691-696
   Abstract »    Full Text »    PDF »
Upregulation of the TLR3 Pathway by Kaposi's Sarcoma-Associated Herpesvirus during Primary Infection.
J. West and B. Damania (2008)
J. Virol. 82, 5440-5449
   Abstract »    Full Text »    PDF »
Analysis of the Neuroinflammatory Response to TLR7 Stimulation in the Brain: Comparison of Multiple TLR7 and/or TLR8 Agonists.
N. B. Butchi, S. Pourciau, M. Du, T. W. Morgan, and K. E. Peterson (2008)
J. Immunol. 180, 7604-7612
   Abstract »    Full Text »    PDF »
Structural Basis of Toll-Like Receptor 3 Signaling with Double-Stranded RNA.
L. Liu, I. Botos, Y. Wang, J. N. Leonard, J. Shiloach, D. M. Segal, and D. R. Davies (2008)
Science 320, 379-381
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882