This Article Full Text Full Text (PDF) All Versions of this Article: jhc.2009.954180v1 57/10/973    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Maximova, O. A. Articles by Pletnev, A. G. PubMed PubMed Citation Articles by Maximova, O. A. Articles by Pletnev, A. G. Social Bookmarking                         What's this?

Cellular Inflammatory Response to Flaviviruses in the Central Nervous System of a Primate Host

Olga A. Maximova, Lawrence J. Faucette, Jerrold M. Ward, Brian R. Murphy and Alexander G. Pletnev

Laboratory of Infectious Diseases (OAM,BRM,AGP) and Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases (LJF,JMW), National Institutes of Health, Bethesda, Maryland

Correspondence to: Olga A. Maximova, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, Room 3W10A, MSC 3203, Bethesda, MD 20892-3203. E-mail: maximovao{at}niaid.nih.gov. Co-corresponding author: Alexander G. Pletnev. E-mail: apletnev{at}niaid.nih.gov

Flaviviruses such as tick-borne encephalitis virus, Japanese encephalitis virus, West Nile virus, and St. Louis encephalitis virus are important neurotropic human pathogens, typically causing a devastating and often fatal neuroinfection. Flaviviruses induce neuroinflammation with typical features of viral encephalitides, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. Development of safe and effective live-virus vaccines against neurotropic flavivirus infections demands a detailed knowledge of their neuropathogenesis in a primate host that is evolutionarily close to humans. Here, we used computerized morphometric analysis to quantitatively assess the cellular inflammatory responses in the central nervous system (CNS) of rhesus monkeys infected with three antigenically divergent attenuated flaviviruses. The kinetics, spatial pattern, and magnitude of microglial activation, trafficking of T and B cells, and changes in T cell subsets within the CNS define unique phenotypic signatures for each of the three viruses. Our results provide a benchmark for investigation of cellular inflammatory responses induced by attenuated flaviviruses in the CNS of primate hosts and provide insight into the neuropathogenesis of flavivirus encephalitis that might guide the development of safe and effective live-virus vaccines. (J Histochem Cytochem 57:973–989, 2009)

Key Words: flaviviruses • non-human primates • central nervous system • cellular inflammatory response • immunohistochemistry • digital whole-tissue section slides • computerized morphometric analysis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Guidelines | Subscriptions | About | exPRESS - Current - Archive | Business Information | Contact

The Journal of Histochemistry & Cytochemistry is owned, published, and licensed by The Histochemical Society © 2009