title: High-throughput automated image analysis of neuroinflammation and neurodegeneration enables quantitative assessment of virus neurovirulence.
abstract: Historically, the safety of live attenuated vaccine candidates against neurotropic viruses was assessed by semi-quantitative analysis of virus-induced histopathology in the central nervous system of monkeys. We have developed a high-throughput automated image analysis (AIA) for the quantitative assessment of virus-induced neuroinflammation and neurodegeneration. Evaluation of the results generated by AIA showed that quantitative estimates of lymphocytic infiltration, microglial activation, and neurodegeneration strongly and significantly correlated with results of traditional histopathological scoring. In addition, we show that AIA is a targeted, objective, accurate, and time-efficient approach that provides reliable differentiation of virus neurovirulence. As such, it may become a useful tool in establishing consistent analytical standards across research and development laboratories and regulatory agencies, and may improve the safety evaluation of live virus vaccines. The implementation of this high-throughput AIA will markedly advance many fields of research including virology, neuroinflammation, neuroscience, and vaccinology.
authors.affiliation: Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD 20892, USA. maximovao@niaid.nih.gov
authors.forename: Olga A
authors.initials: OA
authors.lastname: Maximova
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Pletnev
mesh_terms: D000818:Animals; D001331:Automation / Q000379:methods*; D003716:Dengue Virus / Q000472:pathogenicity; D004669:Encephalitis Viruses, Tick-Borne / Q000472:pathogenicity; D057166:High-Throughput Screening Assays / Q000379:methods*; D006651:Histocytochemistry; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008253:Macaca mulatta; D008853:Microscopy; D009422:Nervous System Diseases / Q000473:pathology* / Q000517:prevention & control / Q000821:virology; D018419:Primate Diseases / Q000473:pathology* / Q000517:prevention & control / Q000821:virology; D014777:Virus Diseases / Q000473:pathology* / Q000517:prevention & control