Molecular characterization of the complete genome of human influenza H5N1 virus isolates from Thailand

Abstract

The complete genomes of three human H5N1 influenza isolates were characterized, together with the haemagglutinin (HA) and neuraminidase (NA) genes from two additional human isolates and one chicken isolate. These six influenza isolates were obtained from four different provinces of Thailand during the avian influenza outbreak in Asia from late 2003 to May 2004. All six Thailand isolates contained multiple basic amino acids at the cleavage site in the HA gene. Amino acid residues at the receptor-binding site of the five human viruses were similar to those of the chicken virus and other H5N1 viruses from Hong Kong. The presence of amantadine resistance in the Thailand viruses isolated during this outbreak was suggested by a fixed mutation in M2 and confirmed by a phenotypic assay. All genomic segments of the Thailand viruses clustered with the recently described genotype Z. The Thailand viruses contained more avian-specific residues than the 1997 Hong Kong H5N1 viruses, suggesting that the virus may have adapted to allow a more efficient spread in avian species.

Differential Host Determinants Contribute to the Pathogenesis of 2009 Pandemic H1N1 and Human H5N1 Influenza A Viruses in Experimental Mouse Models

“…17 We show that C57BL/6J mice are more susceptible to pH1N1 influenza isolates, whereas BALB/c mice are mostly resistant. No differences in susceptibility were observed for seasonal H1N1 influenza in both mouse models.…”

“…HH05, HH15, A/Solomon Islands/3/06-like (H1N1) (seasonal H1N1), and A/Thailand/KAN-1/04 (H5N1) (human H5N1; isolated from a fatal human case 17 ) were grown on Madin-Darby canine kidney cells. All virus strains were passaged only one to two times in MadinDarby canine kidney cells for virus stock generation and sequenced thereafter to exclude potential mutations upon multiple passaging.…”

Virulence determinants of pandemic influenza viruses

“…H5N1 viruses with a PB2 E627K mutation cause a lethal, systemic infection in mice, but become nonpathogenic for mammals if this residue remains a glutamic acid (80). Moreover, avian viruses quickly acquire the E627K change after a single passage in mice (81,82), and many of the H5N1 viruses isolated from human hosts carry a PB2 with E627K (59,83,84).…”

High Susceptibility of Human Dendritic Cells to Avian Influenza H5N1 Virus Infection and Protection by IFN-α and TLR Ligands

“…Moreover, DCs could be protected from H5N1 infection after pretreatment with IFN-␣ and TLR ligands. (16). The titer of virus stock was determined by titration in MDCK and by daily observation for cytopathic effects and was confirmed by a hemagglutination assay.…”