NDLI: Semaphorin 7A contributes to West Nile virus pathogenesis through TGF-ß1/Smad6 signaling.

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Semaphorin 7A contributes to West Nile virus pathogenesis through TGF-ß1/Smad6 signaling.

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Semaphorin 7A contributes to West Nile virus pathogenesis through TGF-ß1/Smad6 signaling.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Medzhitov, Ruslan M. Fikrig, Erol Montgomery, Ruth R. Anderson, John F. Neelakanta, Girish Foellmer, Harald G. Sultana, Hameeda Koski, Raymond A.
Description	Country affiliation: United States Author Affiliation: Sultana H ( Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. hameeda.sultana@yale.edu)
Abstract	Semaphorin 7A (Sema7A) is a membrane-associated/secreted protein that plays an essential role in connecting the vertebrate neuronal and immune systems. However, the role of Sema7A has not been elucidated in viral pathogenesis. In this study, we show that abrogation of Sema7A protects mice from lethal West Nile virus (WNV) infection. Mice lacking Sema7A showed increased survival, reduced viral burden, and less blood-brain barrier permeability upon WNV infection. Increased Sema7A levels were evident in murine tissues, as well as in murine cortical neurons and primary human macrophages upon WNV infection. Treatment with Sema7A Ab blocked WNV infection in both of these cell types. Furthermore, Sema7A positively regulates the production of TGF-ß1 and Smad6 to facilitate WNV pathogenesis in mice. Collectively, these data elucidate the role of Sema7A in shared signaling pathways used by the immune and nervous systems during viral pathogenesis that may lead to the development of Sema7A-blocking therapies for WNV and possibly other flaviviral infections.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1201140
Journal	The Journal of Immunology
Issue Number	6
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Cd Physiology Semaphorins Signal Transduction Immunology Smad6 Protein Transforming Growth Factor Beta1 West Nile Virus Pathogenicity Animals Cell Line Cells, Cultured Cerebral Cortex Metabolism Virology Disease Models, Animal Hek293 Cells Mice Mice, Inbred C57bl Mice, Knockout Virus Replication Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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