Characterization of clade 2.3.4.4 H5N8 highly pathogenic avian influenza viruses from wild birds possessing atypical hemagglutinin polybasic cleavage sites

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• 作者：Tatsufumi Usui ; Kosuke Soda ; Yukiko Tomioka ; Hiroshi Ito ; Toshiyo Yabuta…
• 关键词：Highly pathogenic avian influenza ; H5N8 subtype ; Clade 2.3.4.4 ; Cleavage site ; Wild bird ; Virulence
• 刊名：Virus Genes
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：53
• 期：1
• 页码：44-51
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Medical Microbiology; Virology; Plant Sciences;
• 出版者：Springer US
• ISSN：1572-994X
• 卷排序：53

文摘

Since 2014, clade 2.3.4.4 H5 subtype highly pathogenic avian influenza viruses (HPAIVs) have been distributed worldwide. These viruses, which were reported to be highly virulent in chickens by intravenous inoculation, have a consensus HPAI motif PLRERRRKR at the HA cleavage site. However, two-clade 2.3.4.4 H5N8 viruses which we isolated from wild migratory birds in late 2014 in Japan possessed atypical HA cleavage sequences. A swan isolate, Tottori/C6, had a novel polybasic cleavage sequence, PLGERRRKR, and another isolate from a dead mandarin duck, Gifu/01, had a heterogeneous mixture of consensus PLRERRRKR and variant PLRERRRRKR sequences. The polybasic HA cleavage site is the prime virulence determinant of AIVs. Therefore, in the present study, we examined the pathogenicity of these H5N8 isolates in chickens by intravenous inoculation. When 106 EID<sub>50sub> of these viruses were intravenously inoculated into chickens, the mean death time associated with Tottori/C6 was substantially longer (>6.1 days) than that associated with Gifu/01 (2.5 days). These viruses had comparable abilities to replicate in tissue culture cells in the presence and absence of exogenous trypsin, but the growth of Tottori/C6 was hampered. These results indicate that the novel cleavage motif of Tottori/C6 did not directly affect the infectivity of the virus, but Tottori/C6 caused attenuated pathogenicity in chickens because of hampered replication efficiency. It is important to test for the emergence of diversified HPAIVs, because introduction of HPAIVs with a lower virulence like Tottori/C6 might hinder early detection of affected birds in poultry farms.