Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 28, 1999
Publication Date: February 1, 2000
Interpretive Summary: The avian/human influenza outbreak that occurred in Hong Kong in 1997 produced a unique strain of influenza virus. A purely avian-origin virus infected humans and was associated with severe disease and deaths. It has been shown that this virus is also capable of inducing a lethal infection in mice, without any prior adaptation from the birds. It is not known however whether this mouse lethality is a unique characteristic of the Hon Kong origin viruses or whether other highly pathogenic avian influenza (AI) viruses might also induce such a disease in mammals. This study was undertaken to evaluate the pathogenicity of several highly pathogenic AI viruses and determine whether the mouse infection is an accurate reflection of the human infection. The HK-origin AI isolates are unique in their ability to infect and cause a lethal pneumonia in mice. Unlike the other strains, mice infected with HKAI strains rapidly lost weight and body temperature, and pneumonic lesions persisted and expanded until the mouse died. Also, while other H5 AI strains induced production of an important immunological stimulus, namely the cytokine IFN-beta, the HKAI strains did not. Thus mice allow a ready distinction between two groups of H5 AI viruses that are all lethal in chickens. This clear distinction in pathology may provide a rapid means of testing potential for human infection by avian influenza viruses in future outbreaks.
Technical Abstract: In 1997, an outbreak of virulent H5N1 avian influenza (AI) virus occurred in poultry in Hong Kong (HK) and was linked to the direct transmission of H5N1 virus from infected poultry to humans. In this study, two avian and one human HK-origin H5N1 viruses along with four additional highly pathogenic H5 avian influenza viruses were analyzed for their ability to cause disease in six to eight-week-old BALB/c mice. Both avian and human H H5 influenza isolates caused disease characterized by induced hypothermia, clinical signs, rapid weight loss, and 75-100% mortality by 6 to 8 days post-infection (dpi). Three of the non-HK-origin isolates caused no clinical signs. One isolate, A/tk/England/91 (H5N1), induced disease and all but one of the animals recovered. Infection resulted in mild to severe lesions in the respiratory tract of mice. The viruses caused necrosis in respiratory epithelium of the nasal cavity, trachea, bronchi, and bronchioles with accompanying inflammation. The most severe and widesprea lesions were observed in the lungs of HK AI virus infected mice while no lesions or only mild lesions were evident with viruses from Scotland, Mexico. The A/ck/Italy/97 (H5N2) and the tk/Eng/91 viruses exhibited intermediate pathogenesis, producing mild-to-moderate respiratory tract lesions. The non-HK-origin isolates induced production of increased levels of active TGF-Beta following infection, while HK-origin isolates did not.