The H5N1 viruses isolated from humans in Hong Kong directly infected both mice and ferrets without prior adaptation to either host. Two representative viruses, A/Hong Kong/483/97 (HK/483) and A/Hong Kong/486/97 (HK/486) were equally virulent in outbred ferrets but differed in their virulence in inbred mice. Both HK/483 and HK/486 replicated systemically in ferrets and showed neurologic manifestations. In contrast, intranasal infection of mice with HK/483, but not HK/486, resulted in viral spread to the brain, neurologic signs, and death. However, HK/486 was able to replicate in the brain and induce lethal disease following direct intracerebral inoculation.

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