Virus infection of the CNS disrupts the immune-neural-synaptic axis via induction of pleiotropic gene regulation of host responses
Olga A. Maximova, Daniel E. Sturdevant, John C. Kash, Kishore Kanakabandi, Yongli Xiao, Mahnaz Minai, Ian N. Moore, Jeff Taubenberger, Craig Martens, Jeffrey I. Cohen, Alexander G. Pletnev
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.