| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
¶ ¶
From the Departamentoes de Microbiologia,* Patologia, and Bioquímica e Imunologia, ¶ Universidade Federal de Minas Gerais, Belo Horizonte; the Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brasil; the Laboratory of Viral Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland; and the Department of Host Defense,|| Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Herpes simplex virus 1 (HSV-1), a large DNA virus from the Herpesviridae family, is the major cause of sporadic lethal encephalitis and blindness in humans. Recent studies have shown the importance of Toll-like receptors (TLRs) in the immune response to HSV-1 infection. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein that is downstream to mediated TLR activation and is essential for the production of inflammatory cytokines. Here, we studied the relationship between MyD88 and HSV-1 using a purified HSV-1 isolated from a natural oral recurrent human infection. We observed the activation of TLR-2 by HSV-1 in vitro using Chinese hamster ovary cells stably transfected with a reporter gene. Interestingly, we found that only peritoneal macrophages from MyD88–/– mice, but not macrophages from TRL2–/– or from wild-type mice, were unable to produce tumor necrosis factor-
in response to HSV-1 exposure. Additionally, although TLR2–/– mice showed no enhanced susceptibility to intranasal infection with HSV-1, MyD88–/– mice were highly susceptible to infection and displayed viral migration to the brain, severe neuropathological signs of encephalitis, and 100% mortality by day 10 after infection. Together, our results suggest that innate resistance to HSV-1 is mediated by MyD88 and may rely on activation of multiple TLRs.
This article has been cited by other articles:
 |
|
 |
|
  C. Cermelli, C. F. Orsi, A. Cuoghi, A. Ardizzoni, E. Tagliafico, R. Neglia, S. Peppoloni, and E. Blasi Gene expression profiling of monocytes displaying herpes simplex virus 1 induced dysregulation of antifungal defences J. Med. Microbiol., October 1, 2009; 58(10): 1283 - 1290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Aleyas, J. A. George, Y. W. Han, M. M. Rahman, S. J. Kim, S. B. Han, B. S. Kim, K. Kim, and S. K. Eo Functional Modulation of Dendritic Cells and Macrophages by Japanese Encephalitis Virus through MyD88 Adaptor Molecule-Dependent and -Independent Pathways J. Immunol., August 15, 2009; 183(4): 2462 - 2474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sharma and R. K. Maheshwari Oligonucleotide array analysis of Toll-like receptors and associated signalling genes in Venezuelan equine encephalitis virus-infected mouse brain J. Gen. Virol., August 1, 2009; 90(8): 1836 - 1847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-E. Ariza, R. Glaser, P. T. P. Kaumaya, C. Jones, and M. V. Williams The EBV-Encoded dUTPase Activates NF-{kappa}B through the TLR2 and MyD88-Dependent Signaling Pathway J. Immunol., January 15, 2009; 182(2): 851 - 859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. N. Sorensen, L. S. Reinert, L. Malmgaard, C. Bartholdy, A. R. Thomsen, and S. R. Paludan TLR2 and TLR9 Synergistically Control Herpes Simplex Virus Infection in the Brain J. Immunol., December 15, 2008; 181(12): 8604 - 8612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Welner, R. Pelayo, Y. Nagai, K. P. Garrett, T. R. Wuest, D. J. Carr, L. A. Borghesi, M. A. Farrar, and P. W. Kincade Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection Blood, November 1, 2008; 112(9): 3753 - 3761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ahmad, S. El Bassam, P. Cordeiro, and J. Menezes Requirement of TLR2-mediated signaling for the induction of IL-15 gene expression in human monocytic cells by HSV-1 Blood, September 15, 2008; 112(6): 2360 - 2368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Sheridan and M. A. Beck The Immune Response to Herpes Simplex Virus Encephalitis in Mice Is Modulated by Dietary Vitamin E J. Nutr., January 1, 2008; 138(1): 130 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. P. Sarangi, B. Kim, E. Kurt-Jones, and B. T. Rouse Innate Recognition Network Driving Herpes Simplex Virus-Induced Corneal Immunopathology: Role of the Toll Pathway in Early Inflammatory Events in Stromal Keratitis J. Virol., October 15, 2007; 81(20): 11128 - 11138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Ku, H. von Bernuth, C. Picard, S.-Y. Zhang, H.-H. Chang, K. Yang, M. Chrabieh, A. C. Issekutz, C. K. Cunningham, J. Gallin, et al. Selective predisposition to bacterial infections in IRAK-4 deficient children: IRAK-4 dependent TLRs are otherwise redundant in protective immunity J. Exp. Med., October 1, 2007; 204(10): 2407 - 2422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lundberg, H. Openshaw, M. Wang, H.-J. Yang, and E. Cantin Effects of CXCR3 Signaling on Development of Fatal Encephalitis and Corneal and Periocular Skin Disease in HSV-Infected Mice Are Mouse-Strain Dependent Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4162 - 4170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sato, M. M. Linehan, and A. Iwasaki Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells PNAS, November 14, 2006; 103(46): 17343 - 17348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Lopez, J. S. Yount, and T. M. Moran Toll-Like Receptor-Independent Triggering of Dendritic Cell Maturation by Viruses J. Virol., April 1, 2006; 80(7): 3128 - 3134. [Full Text] [PDF]
|
|
|
|
|
|
R. N. Aravalli, S. Hu, T. N. Rowen, J. M. Palmquist, and J. R. Lokensgard Cutting Edge: TLR2-Mediated Proinflammatory Cytokine and Chemokine Production by Microglial Cells in Response to Herpes Simplex Virus J. Immunol., October 1, 2005; 175(7): 4189 - 4193. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
