Comparison of the pathogenic potential of highly pathogenic avian influenza (HPAI) H5N6, and H5N8 viruses isolated in South Korea during the 2016–2017 winter season

Highly pathogenic avian influenza (HPAI) A(H5N6) and A(H5N8) virus infections resulted in the culling of more than 37 million poultry in the Republic of Korea during the 2016/17 winter season. Here we characterize two representative viruses, A/Environment/Korea/W541/2016 [Em/W541(H5N6)] and A/Common Teal/Korea/W555/2017 [CT/W555(H5N8)], and evaluate their zoonotic potential in various animal models. Both Em/W541(H5N6) and CT /W555(H5N8) are novel reassortants derived from various gene pools of wild bird viruses present in migratory waterfowl arising from eastern China. Despite strong preferential binding to avian virus–type receptors, the viruses were able to grow in human respiratory tract tissues. Em/W541(H5N6) was found to be highly pathogenic in both chickens and ducks, while CT/W555(H5N8) caused lethal infections in chickens but did not induce remarkable clinical illness in ducks. In mice, both viruses appeared to be moderately pathogenic and displayed limited tissue tropism relative to HPAI H5N1 viruses. Em/W541(H5N6) replicated to moderate levels in the upper respiratory tract of ferrets and was detected in the lungs, brain, spleen, liver, and colon. Unexpectedly, two of three ferrets in direct contact with Em/W541(H5N6)-infected animals shed virus and seroconverted at 14 dpi. CT/W555(H5N8) was less pathogenic than the H5N6 virus in ferrets and no transmission was detected. Given the co-circulation of different, phenotypically distinct, subtypes of HPAI H5Nx viruses for the first time in South Korea, detailed virologic investigations are imperative given the capacity of these viruses to evolve and cause human infections.

2016/2017冬季，大韩民国暴发高致病性禽流感（Highly pathogenic avian influenza, HPAI）A(H5N6)与A(H5N8)病毒感染，导致超3700万羽家禽遭到扑杀。本研究针对两株代表性病毒——A/环境/韩国/W541/2016 [Em/W541(H5N6)] 及A/普通凫/韩国/W555/2017 [CT/W555(H5N8)] 开展了病原学表征，并在多种动物模型中评估其人畜共患（zoonotic）潜能。两株病毒Em/W541(H5N6)与CT/W555(H5N8)均为新型重配病毒，其基因片段源自中国东部迁徙水鸟所携带野生鸟类病毒的多样基因库。尽管二者对禽源病毒受体具有强结合偏好性，但仍可在人类呼吸道组织中增殖。研究显示，Em/W541(H5N6)对鸡与鸭均表现出高致病性；而CT/W555(H5N8)可引发鸡只致死性感染，但未在鸭体内诱导显著临床病症。在小鼠模型中，两株病毒均呈中度致病性，相较于HPAI H5N1病毒，其组织嗜性更为局限。Em/W541(H5N6)在雪貂上呼吸道中可达到中度复制水平，并可在其肺、脑、脾、肝及结肠中被检出。出乎意料的是，与Em/W541(H5N6)感染动物直接接触的3只雪貂中，有2只在感染后14天（days post infection, dpi）发生排毒并出现血清阳转。在雪貂模型中，CT/W555(H5N8)的致病性弱于H5N6毒株，且未检测到病毒传播。鉴于韩国首次出现多种表型各异的HPAI H5Nx亚型病毒共同流行，且此类病毒具备进化并引发人类感染的能力，因此开展深入的病毒学研究实属必要。