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Vaccines 2019, 7(1), 19; https://doi.org/10.3390/vaccines7010019

Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains

1
Department of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, Israel
2
Department of Biochemistry and Molecular Genetics, Israel Institute of Biological Research (IIBR), Ness-Ziona, Israel
*
Author to whom correspondence should be addressed.
Authors contributed equally to the article.
Received: 15 November 2018 / Revised: 4 February 2019 / Accepted: 7 February 2019 / Published: 12 February 2019
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Abstract

Viral infections of the central nervous system (CNS) lead to a broad range of pathologies. CNS infections with Orthopox viruses have been mainly documented as an adverse reaction to smallpox vaccination with vaccinia virus. To date, there is insufficient data regarding the mechanisms underlying pathological viral replication or viral clearance. Therefore, informed risk assessment of vaccine adverse reactions or outcome prediction is limited. This work applied a model of viral infection of the CNS, comparing neurovirulent with attenuated strains. We followed various parameters along the disease and correlated viral load, morbidity, and mortality with tissue integrity, innate and adaptive immune response and functionality of the blood–brain barrier. Combining these data with whole brain RNA-seq analysis performed at different time points indicated that neurovirulence is associated with host immune silencing followed by induction of tissue damage-specific pathways. In contrast, brain infection with attenuated strains resulted in rapid and robust induction of innate and adaptive protective immunity, followed by viral clearance and recovery. This study significantly improves our understanding of the mechanisms and processes determining the consequence of viral CNS infection and highlights potential biomarkers associated with such outcomes. View Full-Text
Keywords: vaccinia; brain; meningoencephalitis; smallpox; neurovirulence; RNA-seq vaccinia; brain; meningoencephalitis; smallpox; neurovirulence; RNA-seq
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Israely, T.; Paran, N.; Erez, N.; Cherry, L.; Tamir, H.; Achdout, H.; Politi, B.; Israeli, O.; Zaide, G.; Cohen-Gihon, I.; Vitner, E.B.; Lustig, S.; Melamed, S. Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains. Vaccines 2019, 7, 19.

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