Acute murine H5N1 influenza A encephalitis

Area of Science:

• Virology
• Immunology
• Neuroscience

Background:

• Avian influenza A virus H5N1 (highly pathogenic avian influenza) can infect humans but lacks efficient human-to-human transmission.
• H5N1 infection is linked to neurological disease in avian hosts, animal models, and sporadic human cases.

Purpose of the Study:

• To investigate the immune response during acute encephalitis in mice infected with H5N1.
• To compare the viral infection timeline with immune activation in the central nervous system (CNS) and lungs.

Main Methods:

• BALB/c mice were intranasally infected with H5N1 influenza A/Vietnam/1203/2004.
• Immunohistochemistry and in situ hybridization were used to track viral infection and immune responses.
• Time course analysis of viral detection, neuronal infection, apoptosis, and interferon responses in the lung and CNS.

Main Results:

• H5N1 influenza was detected in the lungs by 1 day postinfection (DPI), while neuronal infection was observed by 4 DPI.
• Infection led to severe acute panencephalitis in mice, with infected neurons showing apoptosis.
• The lungs mounted an early type I interferon (IFN) response, followed by IFN-γ, correlating with reduced viral load.
• The CNS exhibited a blunted type I IFN response compared to the lungs.

Conclusions:

• H5N1 influenza infection in mice causes severe encephalitis with neuronal apoptosis.
• The immune response in the CNS is significantly different from the lungs, characterized by a delayed and blunted type I IFN response.
• These findings highlight the neuroinvasive potential of H5N1 and the distinct immune environment within the CNS during infection.