Jk. Dybing et al., Distinct pathogenesis of hong kong-origin H5N1 viruses in mice compared tothat of other highly pathogenic H5 avian influenza viruses, J VIROLOGY, 74(3), 2000, pp. 1443-1450
In 1997, an outbreak of virulent H5N1 avian influenza virus occurred in pou
ltry in Hong Kong (HK) and was linked to a direct transmission to humans. T
he factors associated with transmission of avian influenza virus to mammals
are not fully understood, and the potential risk of other highly virulent
avian influenza A viruses infecting and causing disease in mammals is not k
nown, In this study, two avian and one human HK-origin H5N1 virus along wit
h four additional highly pathogenic H5 avian influenza viruses were analyze
d for their pathogenicity in 6- to 8-week-old BALB/c mice. Both the avian a
nd human HK H5 influenza virus isolates caused severe disease in mice, char
acterized by induced hypothermia, clinical signs, rapid weight loss, and 75
to 100% mortality by 6 to 8 days postinfection, Three of the non-HK-origin
isolates caused no detectable clinical signs. One isolate, A/tk/England/91
(H5N1), induced measurable disease, and all but one of the animals recover
ed. Infections resulted in mild to severe lesions in both the upper and low
er respiratory tracts, Most consistently, the viruses caused necrosis in re
spiratory epithelium of the nasal cavity, trachea, bronchi, and bronchioles
with accompanying inflammation. The most severe and widespread lesions wer
e observed in the lungs of HK avian influenza virus-infected mice, while no
lesions or only mild lesions were evident with A/ck/Scotland/59 (H5N1) and
A/ck/Queretaro/95 (H5N2), The A/ck/Italy/97 (H5N2) and the A/tk/England/91
(H5N1) viruses exhibited intermediate pathogenicity, producing mild to mod
erate respiratory tract lesions. In addition, infection by the different is
olates could be further distinguished by the mouse immune response. The non
-HK-origin isolates all induced production of increased levels of active tr
ansforming growth factor beta following infection, while the HK-origin isol
ates did not.