Abstract. Three human cases of H10N8 virus infections were initially reported in China in late 2013 and early 2014, two of which were fatal. This was the first time the H10N8 subtype has been detected in humans, and the pathogenicity of this virus remains under characterized. We first assessed its pathogenicity by infecting BALB/c mice with two H10N8 isolates, A/Jiangxi-Donghu/346-1/2013 and A/Chicken/Jiangxi/102/2013. The human isolate (H346-1) demonstrated stronger capability of replication and induced higher cytokine response in vivo than the chicken isolate (C102). In addition, H346-1 was fatal to mice, while all mice (N = 14) in C102-infected group survived during the infection course without weight loss. We hypothesized that the 627K mutation in the PB2 gene (PB2-K627) in H346-1 was associated with high pathogenicity in mice. Taken together, this study based on mouse model provides some insight into understanding the pathogenicity of the emerging viruses in mammals.Avian influenza viruses (AIV) of different subtypes sporadically infect people and cause a wide range of clinical outcomes, from asymptomatic infections to fatal pneumonia.
1AIV is generally considered species specific and rarely crosses the species barrier to infect mammals and humans.2 However, genetic reassortment with different subtypes enables the viruses to infect humans. H6N1, H7N2, H7N3, H7N7, H9N2, and H10N7 viruses have caused conjunctivitis or mild respiratory symptoms, or both, in people, although some severe cases have been reported.3-6 Human infections with avian influenza A H5N1 and H7N9 viruses are more commonly detected and can result in fatal pneumonia.
7Human infections with novel avian influenza A (H10N8) viruses were initially reported in China in December 2013. The infections coincided with the second wave of H7N9 outbreak in mainland China, causing three human cases of infection in Nanchang city with two being fatal. 8 Although the phylogeny and clinical characteristics of H10N8 viruses are clear, the underlying molecular mechanisms for their high pathogenicity in humans remain largely unknown. 8,9 Thus far, no assessment of pathogenicity of H10N8 was reported in any animal model. Here we evaluated this virus's pathogenicity and found that this virus was highly pathogenic in mice.Two H10N8 isolates, human isolate A/Jiangxi-Donghu/346-1/ 2013 (GISAID accession nos: EPI530523-EPI530530) isolated from the first human case, and chicken isolate A/Chicken/ Jiangxi/102/2013 (EPI530539-EPI530546) from chicken in a live poultry market (LPM) that the patient visited, were propagated from 9-day-old specific pathogen-free embryonated chicken eggs. The virus titers and infectivity were determined by EID 50 chicken embryos. In brief, 10-fold serial dilutions of rescued stock viruses were used to inoculate chicken embryos at 37°C for 72 hours. The EID 50 values were calculated by the method of Reed and Muench.10 Fourteen 4-week-old (~12 g) female BALB/c mice of each group were anesthetized with CO 2 and inoculated intranasally with 50 μL...