P031 Pandemic influenza a H1N1 viruses elicit weak cytokine responses in human astrocytic and neuronal cells

Seasonal, pandemic and avian influenza H5N1 virus infections may be associated with pathology in the central nervous system (CNS), albeit with varying frequency and by different mechanisms. Studies have demonstrated that highly pathogenic avian influenza H5N1 and pandemic H1N1 viruses could be detected within the CNS. Seasonal influenza is regularly associated with encephalopathy in Japan and the Far East. With the exception of influenza associated encephalopathy in Japan, there has been little attention paid to the pathogenesis of CNS disease associated with influenza. In particular, the neuropathogenicity of these viruses remains largely unknown. We have previously demonstrated that differentiated human astrocytic and neuronal cells could be infected with H5N1 viruses. Productive virus replication and strong innate immune response with release of proinflammatory cytokines were detected in the H5N1-infected human astrocytic cells. Seasonal influenza viruses replicated as well as H5N1 viruses in these two cell types but induced much weaker cytokine responses. Here, we extended the study to investigate cytokine response and virus replication kinetics of human brain cells infected with two pandemic H1N1 influenza A viruses that were isolated from the respiratory tract of a neurological complicated and a mild case of infection respectively. We found that the two pandemic H1N1 viruses infected both the human astrocytic and neuronal cells but in contrast with H5N1 and seasonal H1N1 viruses, pandemic H1N1 failed to produce progeny viruses efficiently in either infected astrocytes or neurons. Interestingly, both pandemic H1N1 viruses induced very low expression of proinflammatory cytokines including TNF-alpha, IL-6 and type I interferon, IFN-beta which intensity is much lower compared to that induced by seasonal H1N1 virus. Taken together, results here suggest that pandemic H1N1 virus differs from H5N1 and seasonal H1N1 viruses in the ability to produce progeny viruses in infected human astrocytic and neuronal cells. Virus replication kinetics and cytokine expression profile induced by both pandemic H1N1 viruses are similar. In contrast to H5N1 viruses, pandemic H1N1 viruses inhibit the expression of cytokines that might contribute to the pathogenesis of this virus. Viral and host factors related to these differences are now under investigation.