Virus infection of the CNS disrupts the immune-neural-synaptic axis via induction of pleiotropic gene regulation of host responses

Author:

Maximova Olga A1ORCID,Sturdevant Daniel E2,Kash John C1,Kanakabandi Kishore2,Xiao Yongli1,Minai Mahnaz3,Moore Ian N3,Taubenberger Jeff1,Martens Craig2,Cohen Jeffrey I1,Pletnev Alexander G1

Affiliation:

1. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

2. Research Technologies Branch, Genomics Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, United States

3. Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

Abstract

Treatment for many viral infections of the central nervous system (CNS) remains only supportive. Here we address a remaining gap in our knowledge regarding how the CNS and immune systems interact during viral infection. By examining the regulation of the immune and nervous system processes in a nonhuman primate model of West Nile virus neurological disease, we show that virus infection disrupts the homeostasis of the immune-neural-synaptic axis via induction of pleiotropic genes with distinct functions in each component of the axis. This pleiotropic gene regulation suggests an unintended off-target negative impact of virus-induced host immune responses on the neurotransmission, which may be a common feature of various viral infections of the CNS.

Funder

National Institute of Allergy and Infectious Diseases

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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