Abstract
The central nervous system (CNS) is vulnerable to several viral infections including herpes viruses, arboviruses and HIV to name a few. While a rapid and effective immune response is essential to limit viral spread and mortality, this anti-viral response needs to be tightly regulated in order to limit immune mediated tissue damage. This balance between effective virus control with limited pathology is especially important due to the highly specialized functions and limited regenerative capacity of neurons, which can be targets of direct virus cytolysis or bystander damage. CNS infection with the neurotropic strain of mouse hepatitis virus (MHV) induces an acute encephalomyelitis associated with focal areas of demyelination, which is sustained during viral persistence. Both innate and adaptive immune cells work in coordination to control virus replication. While type I interferons are essential to limit virus spread associated with early mortality, perforin, and interferon-γ promote further virus clearance in astrocytes/microglia and oligodendrocytes, respectively. Effective control of virus replication is nonetheless associated with tissue damage, characterized by demyelinating lesions. Interestingly, the anti-inflammatory cytokine IL-10 limits expansion of tissue lesions during chronic infection without affecting viral persistence. Thus, effective coordination of pro- and anti-inflammatory cytokines is essential during MHV induced encephalomyelitis in order to protect the host against viral infection at a limited cost.
Highlights
The central nervous system (CNS) is susceptible to various neurotropic viral infections associated with acute inflammation
This review primarily focuses on encephalomyelitis induced by neurotropic mouse hepatitis virus (MHV), namely the sublethal glia tropic variant of the John Howard Muller MHV strain, designated v2.2-1, and the non-lethal dual liver and neurotropic MHV-A59 strain [5]
A common theme, applying to neurotropic MHV encephalomyelitis, are the protective activities of IFNα/β signaling in limiting initial viral dissemination and predominantly non-cytolytic T cell effector functions in reducing infectious virus load [1, 2]
Summary
The central nervous system (CNS) is susceptible to various neurotropic viral infections associated with acute inflammation. Viral meningitis is overall more clinically benign, whereas encephalitis is associated with clinical evidence of neurological dysfunctions, which can range from behavioral changes to seizures and paralysis Many encephalitic viruses such as insect borne viruses, enteroviruses, and nonendogenous retroviruses can rapidly invade the CNS early following peripheral infection. This review primarily focuses on encephalomyelitis induced by neurotropic MHV, namely the sublethal glia tropic variant of the John Howard Muller MHV strain, designated v2.2-1, and the non-lethal dual liver and neurotropic MHV-A59 strain [5] Both viruses are characterized by an acute encephalomyelitis which resolves into a persistent infection characterized by demyelination and sustained detection of viral RNA in the absence of infectious virus. As demyelination is immune-mediated and neuronal infection is sparse in the v2.21 model, it provides a useful tool to study the dynamics and regulation of antiviral host immune responses associated with ongoing immune-mediated tissue damage balanced by repair during chronic infection
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