Tags

Type your tag names separated by a space and hit enter

Association of innate immune activation with latent Epstein-Barr virus in active MS lesions.
Neurology 2012; 78(1):15-23Neur

Abstract

OBJECTIVE

To determine whether the activation of innate immune responses, which can be elicited by pathogenic and endogenous triggers, is associated with the presence of Epstein-Barr virus (EBV) infection in the multiple sclerosis (MS) brain.

METHODS

White matter postmortem MS (n = 10) and control tissue (n = 11) was analyzed for the expression of the proinflammatory cytokine interferon α (IFNα) by immunohistochemistry and for EBV by using the highly sensitive method of EBV-encoded RNA (EBER) in situ hybridization.

RESULTS

We detected overexpression of IFNα in active areas of white matter MS lesions but not in inactive MS lesions, normal-appearing white matter, or normal brains. The presence of IFNα in macrophages and microglia (expressing human leukocyte antigen class II) is suggestive of local production as part of an acute inflammatory process. Interestingly, EBERs were also specifically detected in areas where IFNα was overexpressed in these preselected active MS lesions. EBER+ cells were also found in CNS lymphoma and stroke cases, but were absent in other control brains. We next addressed a potential mechanism, e.g., the role of EBERs in eliciting IFNα production, and transfected EBERs into human embryonic kidney (HEK) cells. We used HEK cells that stably expressed Toll-like receptor-3, which recognizes double-stranded RNAs, associated with many viral infections. EBERs elicited IFNα production in vitro.

CONCLUSION

These findings suggest that latent EBV infection may contribute to the inflammatory milieu in active MS lesions by activating innate immune responses, e.g., IFNα production. Unraveling the underlying mechanisms may help in uncovering causal pathways and developing better treatment strategies for MS and other neuroinflammatory diseases.

Authors+Show Affiliations

Department of Neuropathology, John Radcliffe Hospital, University of Oxford, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22156987

Citation

Tzartos, J S., et al. "Association of Innate Immune Activation With Latent Epstein-Barr Virus in Active MS Lesions." Neurology, vol. 78, no. 1, 2012, pp. 15-23.
Tzartos JS, Khan G, Vossenkamper A, et al. Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology. 2012;78(1):15-23.
Tzartos, J. S., Khan, G., Vossenkamper, A., Cruz-Sadaba, M., Lonardi, S., Sefia, E., ... Meier, U. C. (2012). Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology, 78(1), pp. 15-23. doi:10.1212/WNL.0b013e31823ed057.
Tzartos JS, et al. Association of Innate Immune Activation With Latent Epstein-Barr Virus in Active MS Lesions. Neurology. 2012 Jan 3;78(1):15-23. PubMed PMID: 22156987.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. AU - Tzartos,J S, AU - Khan,G, AU - Vossenkamper,A, AU - Cruz-Sadaba,M, AU - Lonardi,S, AU - Sefia,E, AU - Meager,A, AU - Elia,A, AU - Middeldorp,J M, AU - Clemens,M, AU - Farrell,P J, AU - Giovannoni,G, AU - Meier,U-C, Y1 - 2011/12/07/ PY - 2011/12/14/entrez PY - 2011/12/14/pubmed PY - 2012/2/9/medline SP - 15 EP - 23 JF - Neurology JO - Neurology VL - 78 IS - 1 N2 - OBJECTIVE: To determine whether the activation of innate immune responses, which can be elicited by pathogenic and endogenous triggers, is associated with the presence of Epstein-Barr virus (EBV) infection in the multiple sclerosis (MS) brain. METHODS: White matter postmortem MS (n = 10) and control tissue (n = 11) was analyzed for the expression of the proinflammatory cytokine interferon α (IFNα) by immunohistochemistry and for EBV by using the highly sensitive method of EBV-encoded RNA (EBER) in situ hybridization. RESULTS: We detected overexpression of IFNα in active areas of white matter MS lesions but not in inactive MS lesions, normal-appearing white matter, or normal brains. The presence of IFNα in macrophages and microglia (expressing human leukocyte antigen class II) is suggestive of local production as part of an acute inflammatory process. Interestingly, EBERs were also specifically detected in areas where IFNα was overexpressed in these preselected active MS lesions. EBER+ cells were also found in CNS lymphoma and stroke cases, but were absent in other control brains. We next addressed a potential mechanism, e.g., the role of EBERs in eliciting IFNα production, and transfected EBERs into human embryonic kidney (HEK) cells. We used HEK cells that stably expressed Toll-like receptor-3, which recognizes double-stranded RNAs, associated with many viral infections. EBERs elicited IFNα production in vitro. CONCLUSION: These findings suggest that latent EBV infection may contribute to the inflammatory milieu in active MS lesions by activating innate immune responses, e.g., IFNα production. Unraveling the underlying mechanisms may help in uncovering causal pathways and developing better treatment strategies for MS and other neuroinflammatory diseases. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/22156987/Association_of_innate_immune_activation_with_latent_Epstein_Barr_virus_in_active_MS_lesions_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=22156987 DB - PRIME DP - Unbound Medicine ER -