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

Vaccines

Ofir Israeli¹  Inbar Cohen-Gihon¹  Galia Zaide¹  Tomer Israely²  Noam Erez²  Lilach Cherry²  Hagit Achdout²  Sharon Melamed²  Hadas Tamir²  Nir Paran²  Boaz Politi²  Shlomo Lustig²  EinatB. Vitner² 

[1] Department of Biochemistry and Molecular Genetics, Israel Institute of Biological Research (IIBR), Ness-Ziona, Israel;Department of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, Israel;

关键词: vaccinia;    brain;    meningoencephalitis;    smallpox;    neurovirulence;    RNA-seq;   

DOI  :  10.3390/vaccines7010019

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown