Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration

TLDR

Highly pathogenic H5N1 avian influenza viruses pose a major pandemic threat, with a 61 % fatality rate in humans and causing acute neurological signs in infected animals. The study aims to investigate the long‑term neurological sequelae of H5N1 infection in survivors. The authors infected C57BL/6J mice with A/Vietnam/1203/04 H5N1 and demonstrated that the virus ascends from the peripheral nervous system into higher CNS regions. In infected mice, persistent microglial activation, α‑synuclein phosphorylation and aggregation, and loss of substantia nigra dopaminergic neurons were observed, indicating that H5N1 infection could trigger protein‑aggregation neurodegenerative disorders such as Parkinson’s and Alzheimer’s.

Abstract

One of the greatest influenza pandemic threats at this time is posed by the highly pathogenic H5N1 avian influenza viruses. To date, 61% of the 433 known human cases of H5N1 infection have proved fatal. Animals infected by H5N1 viruses have demonstrated acute neurological signs ranging from mild encephalitis to motor disturbances to coma. However, no studies have examined the longer-term neurologic consequences of H5N1 infection among surviving hosts. Using the C57BL/6J mouse, a mouse strain that can be infected by the A/Vietnam/1203/04 H5N1 virus without adaptation, we show that this virus travels from the peripheral nervous system into the CNS to higher levels of the neuroaxis. In regions infected by H5N1 virus, we observe activation of microglia and alpha-synuclein phosphorylation and aggregation that persists long after resolution of the infection. We also observe a significant loss of dopaminergic neurons in the substantia nigra pars compacta 60 days after infection. Our results suggest that a pandemic H5N1 pathogen, or other neurotropic influenza virus, could initiate CNS disorders of protein aggregation including Parkinson's and Alzheimer's diseases.