| Summary: | 碩士 === 國立臺灣大學 === 獸醫學研究所 === 106 === Avian influenza virus (AIV) subtype H6 is distributed worldwide since its first identification from turkeys in Massachusetts, USA in 1965. H6 AIVs were identified as potential progenitors of the highly pathogenic H5N1 AIV that emerged in Hong Kong in 1997 and H5N2 AIV in Taiwan in 2004, and these H6 viruses continue to circulate among the bird populations in Asia. To better understand the mammalian-adapted signatures of H6 AIVs in the field of Taiwan, we analyzed the genetic/antigenic relationship, receptor binding specificity, growth kinetics in vitro, polymerase activity, pathogenicity in vivo and immune responses of the H6 chicken isolates identified between 2000 and 2013 in Taiwan. The analyzed H6 AIVs present frequent substitutions in the globular head domain of the HA protein, undergoing antigenic changes, and can be classified into different clades. Notably, the HA and NA proteins of the new clade of chicken isolates share high sequence homology with the H6N1 human isolate identified in 2013 and the dog isolate found in 2014. Most of the H6 chicken isolates carry the molecular signature for mammalian adaptation, ie. the G228S substitution in the HA protein, and the pathogenicity determinant, ie. a 12-14 a.a. deletion in the NA stalk. While most of the studied H6 AIVs retained the binding specificity to the α2,3-linked sialic acid (avian type), some of the recently isolated strains showed moderate binding to the α2,6-linked sialic acid (mammalian type). The growth kinetic studies in vitro exhibited these H6 AIVs can grow efficiently in MDCK cells without prior adaptation. In the polymerase activity assay, the new clade of H6N1 AIV showed significantly higher polymerase activity than the older virus in avian cells. Upon the experimental infection in SPF chickens, the new clade of H6N1 AIV showed enhanced kidney pathogenesis, rapid shedding, and productive virus replication in major organs including the trachea, lung, and kidney. Furthermore, the upregulation of Mx1 gene may play an important role in chicken immune response for viral clearance and in reducing the pathogenicity of viral infections. Collectively, the “human (or dog)-infecting”-like H6N1 strains continue to circulate among domestic chickens and accumulate changes, which pose a clear threat to public health. Therefore, evolution and spread of H6 AIVs should be closely monitored, and safe and effective preventive countermeasures are warranted.
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