Abstract
Genetically similar H5N1 viruses circulating in the avian reservoir exhibit different levels of pathogenicity in mice. In this study, we characterized two highly pathogenic H5N1 avian isolates—A/Hunan/316/2005 (HN05), which is highly pathogenic in mice, and A/Hubei/489/2004 (HB04), which is nonpathogenic. In mammalian cells, HN05 replicates more efficiently than HB04, although both viruses have similar growth kinetics in avian cells. We used reverse genetics to generate recombinant H5N1 strains containing genes from HN05 and HB04 and examined their virulence. HN05 genes encoding the polymerase complex determine pathogenicity and viral replication ability both in vitro and in vivo. The PB2 subunit plays an important role in enhancing viral replication, and the PB1 and PA subunits contribute mainly to pathogenicity in mice. These results can be used to elucidate host-range expansion and the molecular basis of the high virulence of H5N1 viruses in mammalian species.
Highlights
The highly pathogenic H5N1 avian influenza viruses (AIVs) circulating in animal reservoirs represent a significant public health threat
Hematoxylin and eosin (H&E) staining analysis revealed that at 5 dpi, HN05-infected lungs showed extensive interstitial thickening and consolidation with inflammatory cell infiltrations in the alveolar and bronchial regions, whereas Hubei/489/ 2004 (HB04)-infected lungs displayed minimal signs of infection (Fig 2D). These results reveal that the high pathogenicity of HN05 in mice is positively related to enhanced replication and plaque formation in mammalian cells compared with the HB04 virus
H5N1 avian influenza viruses are occasionally transmitted from poultry to humans and pose a grave threat to public health
Summary
The highly pathogenic H5N1 avian influenza viruses (AIVs) circulating in animal reservoirs represent a significant public health threat. In the 1997 Hong Kong H5N1 outbreak, viruses isolated from clinical cases could replicate in mice without adaptation, and their virulence in mice was varied [8,9]. They are not efficiently transmitted among humans, H5N1 viruses can undergo point mutation or gene reassortment to facilitate airborne transmission among ferrets [10,11]. The pathogenicity of influenza viruses is a polygenic trait that includes contributions from genes encoding hemagglutinin (HA), nonstructural protein (NS) and the polymerase complex [12,13,14,15,16,17].
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