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The Immune Response to Herpes Simplex Virus Type 1 Infection in Susceptible Mice is a Major Cause of CNS Pathology Resulting in Fatal Encephalitis

Lundberg, Patric and Ramakrishna, Chandran and Brown, Jeffrey and Tyszka, J. Michael and Hamamura, Mark and Hinton, David R. and Kovats, Susan and Nalcioglu, Orhan and Weinberg, Kenneth and Openshaw, Harry and Cantin, Edouard M. (2008) The Immune Response to Herpes Simplex Virus Type 1 Infection in Susceptible Mice is a Major Cause of CNS Pathology Resulting in Fatal Encephalitis. Journal of Virology, 82 (14). pp. 7078-7088. ISSN 0022-538X. PMCID PMC2446972. doi:10.1128/JVI.00619-08.

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This study was undertaken to investigate possible immune mechanisms in fatal HSV-1 encephalitis (HSE) after HSV-1 corneal inoculation. Susceptible 129S6 (129) but not resistant C57BL/6 (B6) mice developed intense focal inflammatory brainstem lesions of primarily F4/80+ macrophages and Gr-1+ neutrophils detectable by MRI as early as day 6 post infection (PI). Depletion of macrophages and neutrophils significantly enhanced survival of infected 129 mice. Immunodeficient B6 (IL-7R-/-Kitw41/w41) mice lacking adaptive cells (B6-E mice) transplanted with 129 bone marrow showed significantly accelerated fatal HSE compared to B6-E mice transplanted with B6 marrow or control non-transplanted B6-E mice. In contrast, there was no difference in ocular viral shedding in B6-E mice transplanted with 129 bone marrow or B6 bone marrow. Acyclovir treatment of 129 mice beginning day 4 PI (24 h after HSV-1 first reaches the brain stem) reduced nervous system viral titers to undetectable levels but did not alter brainstem inflammation or mortality. We conclude that fatal HSE in 129 mice results from widespread damage in the brainstem caused by destructive inflammatory responses initiated early in infection by massive infiltration of innate cells.

Item Type:Article
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URLURL TypeDescription CentralArticle
Tyszka, J. Michael0000-0001-9342-9014
Cantin, Edouard M.0000-0002-2352-710X
Additional Information:Copyright © 2008, American Society for Microbiology. Received 19 March 2008/Accepted 6 May 2008. Published ahead of print on 14 May 2008. We thank Paula V. Welander and Seung-Jae Jong for technical assistance. This research was supported by grants EY013814 and AI060038 from the National Institutes of Health, National Eye Institute and National Institutes of Allergy and Infectious Diseases, respectively. Supplemental material for this article may be found at
Funding AgencyGrant Number
National Eye InstituteEY013814
National Institute of Allergy and Infectious DiseasesAI060038
Issue or Number:14
PubMed Central ID:PMC2446972
Record Number:CaltechAUTHORS:LUNjvir08
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10571
Deposited By: Archive Administrator
Deposited On:19 May 2008
Last Modified:01 Jun 2023 23:32

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