Characterization of human influenza A (H5N1) virus infection in mice: neuro-, pneumo- and adipotropic infection

Mice (ddY strain, 4 weeks old) were infected intranasally with the H5N1 inf luenza viruses A/Hong Kong/156/97 (HK156) and A/Hong Kong/483/97 (HK483) is olated from humans. HK156 and HK483 required 200 and 5 p.f.u. of virus, res pectively, to give a 50% lethal dose to the mice when the volume of inoculu m was set at 10 mu l. Both viruses caused encephalitis and severe bronchopn eumonia in infected mice. The severity of lung lesions caused by the viruse s was essentially similar, whereas HK483 caused more extensive lesions in t he brain than did HK156. This was supported by the results of virus titrati on of organ homogenates, which showed that the virus titres in brains of HK 483-infected mice were more than 100-fold higher than those of HK156-infect ed mice, while those in lungs were almost equivalent Both viruses were dete cted in homogenates of the heart, liver, spleen and kidney and brood of the infected mice. Virus antigen was detected by immunohistology in the heart and liver, albeit sporadically, but caused no degenerative change in these organs. The antigen was not detected in the thymus, spleen, pancreas, kidne y or gastrointestinal tract. In contrast, virus antigen was found frequentl y in adipose tissues attached to those organs. The adipose tissues showed s evere degenerative change and the virus titres in the tissues were high and comparable to those in lungs. Thus, infection of HK156 and HK483 in our mo use model was pneumo-, neuro- and adipotropic, but not pantropic, Furthermo re, HK483 showed higher neurotropism than HK156, which may account for its higher lethality.