The Origin of Internal Genes Contributes to the Replication and Transmission Fitness of H7N9 Avian Influenza Virus.
The Origin of Internal Genes Contributes to the Replication and Transmission Fitness of H7N9 Avian Influenza Virus.
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DOI：
10.1128/jvi.01290-22
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发表时间：
2022-11-23
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
--
作者：
H9 N2禽流感病毒（AIV）在包括H7N9在内的人畜共患AIV出现期间捐赠了内部基因片段。我们使用反向遗传学方法产生了A/Anhui/1/13（H7N9）和三个包含来自Anhui/13（H7N9）的血凝素和神经氨酸酶以及来自H9 N2 AIV的六个内部基因片段的重组病毒（2：6 H7N9），所述六个内部基因片段属于（i）G1亚群2，（ii）G1亚群3，或（iii）BJ 94谱系，在整个亚洲的不同地区流行。用含有G1样H9 N2内部基因的2：6 H7 N9感染鸡可在体内产生减毒作用，减少脱落和向接触鸡的传播。然而，拥有BJ 94样H9 N2内部基因导致更快的传播和显着增加泄殖腔脱落相比，父母安徽/13 H7N9。体外分析表明，与安徽/13 H7N9相比，具有BJ 94样内部基因的2：6 H7N9在鸡细胞中的复制显著增加。随后进行了体内共感染实验，其中鸡与成对的安徽/13 H7N9和2：6 H7N9疫苗共感染。在随后的传播事件中，安徽/13 H7N9病毒以2：6的比例战胜了具有BJ 94样或G1样H9 N2病毒内部基因片段的H7N9 AIV。共感染确实导致出现了新的抗性基因型，这些基因型被传播给接触鸡。与祖细胞相比，一些重组病毒在鸡和人细胞中具有更大的复制。我们证明了内部基因盒决定了H7N9病毒在鸡中的传播适应性，并且重配事件可以产生新的H7N9基因型，其在鸡中的毒力增加，人畜共患潜力增强。重要性H9 N2禽流感病毒（AIV）在不同地理区域的家禽中流行。这些病毒的内部基因可以与其他人畜共患禽流感病毒交换，最值得注意的是A/Anhui/1/2013-谱系H7N9，这可能会产生新的病毒基因型，增加对家禽和人类的兽医，经济和公共卫生威胁。我们研究了H9 N2病毒（G1或BJ 94）内部基因在产生新的抗H7N9 AIV中的倾向。我们观察到，H7N9的内部基因，这是BJ 94-like H9 N2病毒的衍生物相比，从G1-like H9 N2病毒具有适应性优势，在鸡之间的有效传播。我们还观察到在鸡传播过程中产生的新的重组病毒，其在人细胞中有效地感染和复制。因此，这种新出现的抗性基因型可能会造成更高的人畜共患病威胁。
H9N2 avian influenza viruses (AIVs) have donated internal gene segments during the emergence of zoonotic AIVs, including H7N9. We used reverse genetics to generate A/Anhui/1/13 (H7N9) and three reassortant viruses (2:6 H7N9) which contained the hemagglutinin and neuraminidase from Anhui/13 (H7N9) and the six internal gene segments from H9N2 AIVs belonging to (i) G1 subgroup 2, (ii) G1 subgroup 3, or (iii) BJ94 lineages, enzootic in different regions throughout Asia. Infection of chickens with the 2:6 H7N9 containing G1-like H9N2 internal genes conferred attenuation in vivo, with reduced shedding and transmission to contact chickens. However, possession of BJ94-like H9N2 internal genes resulted in more rapid transmission and significantly elevated cloacal shedding compared to the parental Anhui/13 H7N9. In vitro analysis showed that the 2:6 H7N9 with BJ94-like internal genes had significantly increased replication compared to the Anhui/13 H7N9 in chicken cells. In vivo coinfection experiments followed, where chickens were coinfected with pairs of Anhui/13 H7N9 and a 2:6 H7N9 reassortant. During ensuing transmission events, the Anhui/13 H7N9 virus outcompeted 2:6 H7N9 AIVs with internal gene segments of BJ94-like or G1-like H9N2 viruses. Coinfection did lead to the emergence of novel reassortant genotypes that were transmitted to contact chickens. Some of the reassortant viruses had a greater replication in chicken and human cells compared to the progenitors. We demonstrated that the internal gene cassette determines the transmission fitness of H7N9 viruses in chickens, and the reassortment events can generate novel H7N9 genotypes with increased virulence in chickens and enhanced zoonotic potential. IMPORTANCE H9N2 avian influenza viruses (AIVs) are enzootic in poultry in different geographical regions. The internal genes of these viruses can be exchanged with other zoonotic AIVs, most notably the A/Anhui/1/2013-lineage H7N9, which can give rise to new virus genotypes with increased veterinary, economic and public health threats to both poultry and humans. We investigated the propensity of the internal genes of H9N2 viruses (G1 or BJ94) in the generation of novel reassortant H7N9 AIVs. We observed that the internal genes of H7N9 which were derivative of BJ94-like H9N2 virus have a fitness advantage compared to those from the G1-like H9N2 viruses for efficient transmission among chickens. We also observed the generation of novel reassortant viruses during chicken transmission which infected and replicated efficiently in human cells. Therefore, such emergent reassortant genotypes may pose an elevated zoonotic threat.
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人类感染新型禽源甲型流感 (H7N9) 病毒。
影响因子：
158.5
作者：
Gao, Rongbao;Cao, Bin;Shu, Yuelong
通讯作者：
Shu, Yuelong
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DOI：
10.1093/emph/eoy013
发表时间：
2018
期刊：
Evolution, medicine, and public health
影响因子：
--
作者：
Bailey ES;Choi JY;Fieldhouse JK;Borkenhagen LK;Zemke J;Zhang D;Gray GC
通讯作者：
Gray GC
影响因子：
5.4
作者：
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通讯作者：
Iqbal M
影响因子：
5.4
作者：
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通讯作者：
Zhang, Chiyu
影响因子：
5.4
作者：
Clements AL;Sealy JE;Peacock TP;Sadeyen JR;Hussain S;Lycett SJ;Shelton H;Digard P;Iqbal M
通讯作者：
Iqbal M