6.2 H5N1 avian influenza In a simplified neurovirulence model, Park et al. (2002) demonstrated that simple intranasal instillation of influenza A (H5N1) virus isolated from a patient during the 1997 Hong Kong outbreak could result in the infection of the murine central nervous system. After initial replication in the respiratory mucosa, the virus apparently traveled through afferent fibers of the olfactory, vagal, trigeminal, and sympathetic nerves, where it was detected by immunohistochemical and in situ hybridization. This study demonstrates the feasibility of using intranasal installation of viruses isolated directly from patients to establish an encephalitis-like infection, an ideal way for quickly evaluating antiviral inhibitors. Yun et al. (2008) injected peramivir intramuscularly into ferrets infected intranasally with the highly neurovirulent A/Vietnam/1203/04 (H5N1) influenza virus and were able to show that peramavir delivered in this manner ameliorated virus-induced disease by reducing infectious virus titers in the lungs and brains and promoted survival in ferrets.