Characterization of a human H5N1 influenza A virus isolated in 2003

Abstract

In 2003, H5N1 avian influenza virus infections were diagnosed in two Hong Kong residents who had visited the Fujian province in mainland China, affording us the opportunity to characterize one of the viral isolates, A/Hong Kong/213/03 (HK213; H5N1). In contrast to H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong, HK213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide chains at the globular head of the hemagglutinin molecule. It demonstrated weak pathogenicity in mice and ferrets but caused lethal infection in chickens. The original isolate failed to produce disease in ducks but became more pathogenic after five passages. Taken together, these findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens. This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans.

FIG. 1.

Receptor specificity of the HK213 virus. (A) The solid-phase binding assay with competing glycopolymers was performed as described in a previous report (14). The binding of HK213 virus to fetuin was not inhibited by a polymer possessing either an α(2,3)- or an α(2,6)-linked sialic acid, unlike the human and avian viruses used as controls for α2,3 or α2,6 binder, respectively. (B) The direct binding activity of viruses to gangliosides was determined by a previously published method (28). The HK213 virus has the ability to bind to both the α(2,3)- and α(2,6)-linked sialic acids.

FIG. 2.

Representative histologic and immunohistologic findings on animals infected with HK213Egg virus. Chickens: detection of viral antigens (brown) in macrophages in the spleen (A), cardiac myocytes (B), and brain tissue (C) on day 2 p.i. Ducks: severe infiltration of mononuclear cells into the lamina propria mucosae of the trachea (D) and focal pneumonia with prominent infiltration of mononuclear cells (E) in asymptomatic animals and brain lesions with prominent viral antigen expression in the dead duckling (F). Mice: antigen-positive cells along the bronchial epithelium on day 3 p.i. (G). Ferrets: perivascular infiltrations of mononuclear cells in the olfactory bulb (H). The boxed area in panel H is shown at a higher magnification in panel I.