Genetic and biological properties of H10N3 avian influenza viruses: A potential pandemic candidate?

Abstract

The continued emergence of human illness caused by avian influenza viruses (AIVs) demonstrates the threat of strains such as H5N1, H7N9, H10N8, and now H10N3. The genetic and biological properties of H10N3 viruses are not fully understood. In this study, three H10N3 strains isolated from live poultry markets (LPMs) were systematically studied. Genome sequencing showed that the poultry‐origin viruses are highly homologous to the human H10N3 isolate. The three avian strains were A/chicken/Jiangsu/0146/2021(abbreviated as JS146, H10N3), A/chicken/Jiangsu/0169/2021 (JS169, H10N3), and A/chicken/Jiangsu/0189/2021(JS189, H10N3). Animal studies indicated that all three viruses are highly pathogenic to mice and that all could replicate efficiently in mouse nasal turbinate and lungs despite maintaining their avian receptor binding affinity. We also found that these viruses replicated efficiently in A549 cells and chicken embryos. The strain JS146 had sensitivity to the neuraminidase‐targeting drugs oseltamivir and zanamivir, whereas JS169 and JS189 were more resistant; genetic comparison implied that a substitution at NA position 368 conferred drug resistance. Importantly, several key molecular markers associated with mammalian adaptation had been detected in both avian and human‐isolated H10N3 influenza viruses in the HA (G228S), PB2 (I292V and A588V), PB1 (M317V and I368V), and PA (A343S, K356R and S409N) protein. The above work contributes new insight into the biology of this potentially zoonotic subtype and provides evidence supporting the continued epidemiological monitoring of human infections caused by AIV subtype H10N3.

Genetic analysis and biological characterization of H10N3 influenza A viruses isolated in China from 2014 to 2021

“…Liu et al 44 reported that dual receptor‐binding properties were maintained in their two H10N3 isolates bearing HA Q222R and G228S. In Guo's study and ours, all H10N3 viruses with HA Q222R and G228S showed higher affinity for avian‐type receptors than for human‐type receptors, 22 except for one H10N3 isolate (CK/FJ/S1254/2021), which displayed a higher affinity for human‐type receptors in our study (Figure 4G). The existence of H10N3 viruses with increased affinity for human‐type receptors highlights the potential threat of those viruses to humans.…”

“…Then, in 2021, an H10N3 human case was reported in Jiangsu, China, raising the concern of cross-species transmission of H10 virus. 10,[21][22][23] This case raised questions as to how the H10N3 virus has evolved to infect humans since 2014, and how much risk do H10N3 viruses pose to the poultry industry and public health. To answer these questions, we conducted extensive studies analyzing the genetics, receptor binding properties, replication, and transmissibility of a series of H10N3 viruses isolated in China from 2014 to 2021.…”

Diversity of genotypes and pathogenicity of H9N2 avian influenza virus derived from wild bird and domestic poultry

“…The genotype S strain CK-74 induced more severe injury to internal organs compared to the genotype A strain CC-3. The differences in amino acid mutations between the two strains were analyzed, among which nine key mutations, including I 292 V (PB2 protein), K 356 R (PA protein), and I 353 V (NP protein) are associated with increased virulence or replication efficiency (Naffakh et al, 2008;Xu et al, 2016;Guo et al, 2022) (Table 2). These specific amino acid mutations may contribute to the pronounced pathological changes observed in the genotype S isolate.…”

“…Conversely, isolates derived from wild birds did not manifest these mutations. These genetic alterations may potentially augment viral replication efficiency within host cells by increasing polymerase activity, consequently contributing to increased virulence (Naffakh et al, 2008;Xu et al, 2016;Guo et al, 2022).…”

Influenza Viruses and Vaccines: The Role of Vaccine Effectiveness Studies for Evaluation of the Benefits of Influenza Vaccines

“…As yet, however, there is no evidence of sustained human-to-human transmission, and human infections are unusual. Nevertheless, careful monitoring is crucial in order to promptly identify viral changes and transmission patterns that could make the virus a threat to humans [ 34 , 41 , 42 , 43 , 44 ].…”