No abstract

Influenza A virus-associated encephalopathy triggered by influenza virus infection often occurs in children aged five and younger in Japan. However, the mechanisms behind Influenza A virus-associated encephalopathy are not yet well understood. This study developed an Influenza A virus-associated encephalopathy-like model using mice infected with Influenza A virus and given lipopolysaccharide treatment. The results showed that the mice used in the model suffered from brain edemas nearly three times more severe, as well as having higher cytokine levels in sera compared to those of the control groups. Using gene expression profiling, cytokine-related genes were found not to be up-regulated in the brain in situ, while protein coding genes, which are known to be involved in blood-brain barrier disruption, were up-regulated. Categorizing the functional groups using gene ontology revealed the terms "ion channels," "calcium oscillation," and "membrane transporter activities." The blood-brain barrier disruption found in this Influenza A virus-associated encephalopathy model can therefore be assumed to be due to a cellular electrolyte imbalance of the neuronal tissue, in addition to a cytokine storm.

In 2001, the 11th influenza A viral protein PB1-F2 was detected and found to be encoded by an alternative open reading frame in the PB1 polymerase gene. PB1-F2 has several unique functions, including roles in promoting apoptosis, increasing inflammation, and regulating viral polymerase activity. This study focused on a single PB1-F2 function: regulation of polymerase activity. We constructed a minigenome system to determine the influence of PB1-F2 amino acid (aa) mutations on polymerase activity. We examined four types of aa mutations: three species-specific aa mutations and one mutation that alters pathogenicity in mice. We discovered that an arginine (R) residue at aa position 29 is highly conserved in avian-derived virus strains. Introducing this mutation into mammalian strain A/WSN/33 (H1N1) led to a marked increase in polymerase activity in mammalian cells.These findings suggest that as PB1-F2 in H5N1 viruses regulates viral polymerase activity, it could be targeted for control of avian influenza infection and drug discovery.