Avian influenza A H7N9 virus infects human astrocytes and neuronal cells and induces inflammatory immune responses
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Seasonal, pandemic, and avian influenza virus infections may be associated with central nervous system pathology, albeit with varying frequency and different mechanisms. Here, we demonstrate that differentiated human astrocytic (T98G) and neuronal (SH-SY5Y) cells can be infected by avian H7N9 and pandemic H1N1 viruses. However, infectious progeny viruses can only be detected in H7N9 virus infected human neuronal cells. Neither of these viral strains can generate infectious progeny virus in human astrocytes despite replication of viral genome was observed. Furthermore, H7N9 virus triggered high pro-inflammatory cytokine expression, while pandemic H1N1 virus induced only low cytokine expression in either brain cell type. The experimental finding here is the first data to demonstrate that avian H7N9 virus can infect, transcribe, and replicate its viral genome; induce cytokine upregulation; and cause cytopathic effects in human brain cells, which may potentially lead to profound central nervous system injury. Observation for neurological problems due to H7N9 virus infection deserves further attention when managing these patients.
KeywordsCytokines Neuroinflammation Encephalitis Encephalopathy Neurodegenerative diseases Neurological complications
The authors thank Mr. Li Ping-hung, Ms. Aisha Selim, and Ms. Li Shu-ting for their technical support, Dr. Fanny Ip for the helpful discussion, and Ms. Capucine Jacob-Chavagnac for revising the manuscript.
This research was supported in part by Hong Kong Research Grants Council (HKUST 1/06C), Area of Excellence Scheme (AoE/B-15/01 and AoE/M-12/06), Theme-based Research Scheme (T11-705/14-N), Health and Medical Research Fund (12111822 and 14130662), and Hong Kong Jockey Club, and Roche R&D Center (China) Ltd. (RRDCCL12SC01).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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