Abstract
Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Although the H5N8 virus has been only moderately pathogenic to mammalian hosts, virulence can still increase. We evaluated the pathogenic potential of several H5N8 strains via the mouse-adaptation method. Two H5N8 viruses were sequentially passaged in BALB/c mice and plaque-purified from lung samples. The viruses rapidly obtained high virulence (MLD50, up to 0.5 log10 PFU/mL) within 5 passages. Sequence analysis revealed the acquisition of several virulence markers, including the novel marker P708S in PB1 gene. Combinations of markers synergistically enhanced viral replication and polymerase activity in human cell lines and virulence and multiorgan dissemination in mice. These results suggest that H5N8 viruses can rapidly acquire virulence markers in mammalian hosts; thus, rapid spread as well as repeated viral introduction into the hosts may significantly increase the risk of human infection and elevate pandemic potential.
Highlights
Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health
Since the highly pathogenic avian influenza (HPAI) H5N1 virus was first isolated in China in 19961, these viruses have maintained stable serotypic combinations between the haemagglutinin (HA) and neuraminidase (NA) genes, though they are genetically divided into 10 distinct clades (0–9) based on the divergence of the HA gene[2]
Increased morbidity was still observed in P5 mice, even at a low-inoculation dosage (10,000-fold diluted from lung homogenate of P4 mice). These results indicate that H5N8 viruses can achieve virulence in mice within 5 passages
Summary
Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Combinations of markers synergistically enhanced viral replication and polymerase activity in human cell lines and virulence and multiorgan dissemination in mice. These results suggest that H5N8 viruses can rapidly acquire virulence markers in mammalian hosts; rapid spread as well as repeated viral introduction into the hosts may significantly increase the risk of human infection and elevate pandemic potential. Adaptive mutations, including T97I, K142E, and I353R, in avian-originated PA genes contribute to enhanced polymerase activity and viral replication in mammalian cells and hosts[16,23,24]. A combination of the mutations synergistically enhances avian influenza virulence and replicative efficiency in mammalian hosts in vitro and in vivo[25,26].
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