Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice.

The A/VN/1203/04 strain of the H5N1 influenza virus is capable of infecting the
CNS of mice and inducing a number of neurodegenerative pathologies. Here, we
examined the effects of H5N1 on several pathological aspects affected in
parkinsonism, including loss of the phenotype of dopaminergic neurons located in
the substantia nigra pars compacta (SNpc), expression of monoamines and
indolamines in brain, alterations in SNpc microglia number and morphology, and
expression of cytokines, chemokines, and growth factors. We find that H5N1
induces a transient loss of the dopaminergic phenotype in SNpc and now report
that this loss recovers by 90 d after infection. A similar pattern of loss and
recovery was seen in monoamine levels of the basal ganglia. The inflammatory
response in lung and different regions of the brain known to be targets of the
H5N1 virus (brainstem, substantia nigra, striatum, and cortex) were examined at
3, 10, 21, 60, and 90 d after infection. In each of these brain regions, we found
a significant increase in the number of activated microglia that lasted at least
90 d. We also quantified expression of IL-1α, IL-1β, IL-2, IL-6, IL-9, IL-10,
IL-12(p70), IL-13, TNF-α, IFN-γ, granulocyte-macrophage colony-stimulating
factor, granulocyte colony-stimulating factor, macrophage colony-stimulating
factor, eotaxin, interferon-inducible protein 10, cytokine-induced neutrophil
chemoattractant, monocyte chemotactic protein-1, macrophage inflammatory protein
(MIP) 1α, MIP-1β, and VEGF, and found that the pattern and levels of expression
are dependent on both brain region and time after infection. We conclude that
H5N1 infection in mice induces a long-lasting inflammatory response in brain and
may play a contributing factor in the development of pathologies in
neurodegenerative disorders.