PDF(Pubmed)
Abstract：
Between 2013 and 2017, the A/Anhui/1/13-lineage (H7N9) low-pathogenicity avian influenza virus (LPAIV) was epizootic in chickens in China, causing mild disease, with 616 fatal human cases. Despite poultry vaccination, H7N9 has not been eradicated. Previously, we demonstrated increased pathogenesis in turkeys infected with H7N9, correlating with the emergence of the L217Q (L226Q H3 numbering) polymorphism in the haemagglutinin (HA) protein. A Q217-containing virus also arose and is now dominant in China following vaccination. We compared infection and transmission of this Q217-containing \'turkey-adapted\' (ty-ad) isolate alongside the H7N9 (L217) wild-type (wt) virus in different poultry species and investigated the zoonotic potential in the ferret model. Both wt and ty-ad viruses demonstrated similar shedding and transmission in turkeys and chickens. However, the ty-ad virus was significantly more pathogenic than the wt virus in turkeys but not in chickens, causing 100 and 33% mortality in turkeys respectively. Expanded tissue tropism was seen for the ty-ad virus in turkeys but not in chickens, yet the viral cell receptor distribution was broadly similar in the visceral organs of both species. The ty-ad virus required exogenous trypsin for in vitro replication yet had increased replication in primary avian cells. Replication was comparable in mammalian cells, and the ty-ad virus replicated successfully in ferrets. The L217Q polymorphism also affected antigenicity. Therefore, H7N9 infection in turkeys can generate novel variants with increased risk through altered pathogenicity and potential HA antigenic escape. These findings emphasize the requirement for enhanced surveillance and understanding of A/Anhui/1/13-lineage viruses and their risk to different species.
摘要：
在2013年至2017年期间，A/安徽/1/13谱系（H7N9）低致病性禽流感病毒（LPAIV）在中国鸡体内流行，导致轻度疾病，有616例人类死亡病例.尽管接种了家禽疫苗，H7N9尚未根除。以前,我们证明了感染H7N9的火鸡的发病机制增加,这与血凝素(HA)蛋白中L217Q(L226QH3编号)多态性的出现相关.在接种疫苗后，还出现了一种含Q217的病毒，目前在中国占主导地位。我们比较了这种含Q217的“适应火鸡”（ty-ad）分离株与H7N9（L217）野生型（wt）病毒在不同家禽物种中的感染和传播，并研究了雪貂模型中的人畜共患潜力。wt和ty-ad病毒在火鸡和鸡中都表现出相似的脱落和传播。然而,在火鸡中，ty-ad病毒的致病性明显高于wt病毒，但在鸡中却没有，在火鸡中分别造成100%和33%的死亡率。在火鸡中发现了ty-ad病毒的组织嗜性扩大，但在鸡中却没有。然而，两种物种的内脏器官中的病毒细胞受体分布大致相似。ty-ad病毒需要外源胰蛋白酶进行体外复制，但在原代禽类细胞中的复制增加。在哺乳动物细胞中复制相当，ty-ad病毒在雪貂中成功复制。L217Q多态性也影响抗原性。因此,火鸡中的H7N9感染可以通过改变的致病性和潜在的HA抗原逃逸产生具有增加的风险的新变体。这些发现强调了加强对A/安徽/1/13谱系病毒及其对不同物种的风险的监测和了解的要求。
