Coinfection of Chickens with H9N2 and H7N9 Avian Influenza Viruses Leads to Emergence of Reassortant H9N9 Virus with Increased Fitness for Poultry and a Zoonotic Potential.
Coinfection of Chickens with H9N2 and H7N9 Avian Influenza Viruses Leads to Emergence of Reassortant H9N9 Virus with Increased Fitness for Poultry and a Zoonotic Potential.
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DOI：
10.1128/jvi.01856-21
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发表时间：
2022-03-09
影响因子：
5.4
通讯作者：
Iqbal M
中科院分区：
文献类型：
--
作者：
Bhat S;James J;Sadeyen JR;Mahmood S;Everest HJ;Chang P;Walsh SK;Byrne AMP;Mollett B;Lean F;Sealy JE;Shelton H;Slomka MJ;Brookes SM;Iqbal M
H7N9低致病性禽流感病毒（LPAIV）于2013年通过H9 N2与中国鸟类中传播的其他LPAIV之间的基因重配而出现。这种病毒在鸡中引起不明显的临床疾病，但人畜共患传播导致人类严重和致命的疾病。为了研究在印度次大陆占优势的H7N9和G1谱系H9 N2病毒之间的自然重配情况，我们用A/Anhui/1/2013/H7N9（Anhui/13）病毒和A/Chicken/Pakistan/UDL-01/2008/H9 N2（UDL/08）病毒进行了鸡的实验性共感染。对经接触鸡口咽部流出的残留病毒进行空斑纯化和基因分型，结果显示H9 N2和H9 N9为主要亚型。接触性鸡群释放的病毒也表现出H9 N2病毒聚合酶基因的选择性富集。成功地从接触鸡的口咽部脱落了活的“6+2”抗性株H9 N9（具有来自H7N9的核蛋白[NP]和神经氨酸酶[NA]以及来自H9 N2的其余基因），并且与H9 N2相比，它显示出在人A549细胞中增加的复制率以及与α 2，6和α 2，3唾液酸聚糖的显著更高的受体结合。与H7N9病毒相比，H9 N9病毒的融合pH值也较低，在直接感染的雪貂中以相似的水平复制，并通过直接接触传播。与H7N9气溶胶接触雪貂相比，通过气溶胶接触H9 N9的雪貂也被发现血清反应阳性。据我们所知，这是第一项研究表明，H7N9和G1谱系H9 N2病毒的共循环可能对产生新的可抵抗H9 N9病毒构成威胁，这些病毒在家禽中具有更大的毒力和人畜共患潜力。我们评估了H7N9和G1谱系的当代H9 N2病毒之间重配的后果，这些病毒在印度次大陆和中东的家禽中流行。鸡与这些病毒的共感染导致了具有来自H9 N2和H7N9病毒的基因的新的可抵抗的H9 N9病毒的出现。“6+2”亚型H9 N9（具有来自H7N9的NP和NA）病毒与大多数亚型病毒相比以显著更高的比例从接触鸡中脱落，在人A549细胞中显示出显著增加的复制适应性，与人（α 2，6）和禽（α 2，3）唾液酸受体类似物的受体结合，以及通过雪貂之间的接触传播的潜力。这项研究证明了自然界中已经存在的病毒交换遗传物质的能力，强调了这些亚型病毒可能出现的人畜共患病潜力。
An H7N9 low-pathogenicity avian influenza virus (LPAIV) emerged in 2013 through genetic reassortment between H9N2 and other LPAIVs circulating in birds in China. This virus causes inapparent clinical disease in chickens, but zoonotic transmission results in severe and fatal disease in humans. To examine a natural reassortment scenario between H7N9 and G1 lineage H9N2 viruses predominant in the Indian subcontinent, we performed an experimental coinfection of chickens with A/Anhui/1/2013/H7N9 (Anhui/13) virus and A/Chicken/Pakistan/UDL-01/2008/H9N2 (UDL/08) virus. Plaque purification and genotyping of the reassortant viruses shed via the oropharynx of contact chickens showed H9N2 and H9N9 as predominant subtypes. The reassortant viruses shed by contact chickens also showed selective enrichment of polymerase genes from H9N2 virus. The viable “6+2” reassortant H9N9 (having nucleoprotein [NP] and neuraminidase [NA] from H7N9 and the remaining genes from H9N2) was successfully shed from the oropharynx of contact chickens, plus it showed an increased replication rate in human A549 cells and a significantly higher receptor binding to α2,6 and α2,3 sialoglycans compared to H9N2. The reassortant H9N9 virus also had a lower fusion pH, replicated in directly infected ferrets at similar levels compared to H7N9 and transmitted via direct contact. Ferrets exposed to H9N9 via aerosol contact were also found to be seropositive, compared to H7N9 aerosol contact ferrets. To the best of our knowledge, this is the first study demonstrating that cocirculation of H7N9 and G1 lineage H9N2 viruses could represent a threat for the generation of novel reassortant H9N9 viruses with greater virulence in poultry and a zoonotic potential. IMPORTANCE We evaluated the consequences of reassortment between the H7N9 and the contemporary H9N2 viruses of the G1 lineage that are enzootic in poultry across the Indian subcontinent and the Middle East. Coinfection of chickens with these viruses resulted in the emergence of novel reassortant H9N9 viruses with genes derived from both H9N2 and H7N9 viruses. The “6+2” reassortant H9N9 (having NP and NA from H7N9) virus was shed from contact chickens in a significantly higher proportion compared to most of the reassortant viruses, showed significantly increased replication fitness in human A549 cells, receptor binding toward human (α2,6) and avian (α2,3) sialic acid receptor analogues, and the potential to transmit via contact among ferrets. This study demonstrated the ability of viruses that already exist in nature to exchange genetic material, highlighting the potential emergence of viruses from these subtypes with zoonotic potential.
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