Highly Pathogenic Avian Influenza H5N1 Virus Infections in Wild Red Foxes (Vulpes vulpes) Show Neurotropism and Adaptive Virus Mutations.
Highly Pathogenic Avian Influenza H5N1 Virus Infections in Wild Red Foxes (Vulpes vulpes) Show Neurotropism and Adaptive Virus Mutations.
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DOI：
10.1128/spectrum.02867-22
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发表时间：
2023-02-14
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
2020年至2022年高致病性禽流感病毒（HPAI）流行期间，欧洲报告了数起哺乳动物感染病例。在荷兰，在 2021 年 12 月至 2022 年 2 月期间出现神经系统症状的三只野生红狐（Vulpes vulpes）中检测到 HPAI H5N1 病毒感染。组织病理学分析表明，该病毒主要存在于大脑中，在呼吸道或其他器官中检测到有限或未检测到。在喉咙和直肠拭子中观察到有限的病毒脱落或没有观察到病毒脱落。系统发育分析表明，这三种狐狸病毒并不密切相关，但它们与野生鸟类中发现的 HPAI H5N1 clade 2.3.4.4b 病毒有关。这表明病毒并未在狐狸之间传播。遗传分析表明，两种狐狸病毒的聚合酶碱性二 (PB2) 蛋白中存在哺乳动物适应 E627K。在两只狐狸中，禽类（PB2-627E）和哺乳动物（PB2-627K）变体以混合物形式存在于病毒群体中，这表明该突变出现在这些特定动物中。分离出两种变异病毒，并进行病毒复制和传代实验。这些实验表明，与鸡细胞系相比，PB2-627K 突变增加了哺乳动物细胞系中病毒的复制，并且在哺乳动物上呼吸道的较低温度下。这项研究表明，HPAI H5N1 病毒能够适应哺乳动物；然而，需要更多的适应性突变才能实现哺乳动物之间的有效传播。因此，应扩大对哺乳动物的监测，密切监测人畜共患突变的出现，以做好大流行的准备。重要性 2021 年至 2022 年，高致病性禽流感 (HPAI) 病毒导致荷兰野生鸟类高死亡率。最近，三只野生狐狸被发现感染了 HPAI H5N1 病毒，可能是由于狐狸以受感染的鸟类为食。尽管高致病性禽流感是一种呼吸道病毒，但在这些狐狸身上，病毒主要是在大脑中检测到的。从狐狸身上分离出的两种病毒含有与适应哺乳动物有关的突变。我们发现，突变病毒在哺乳动物细胞中比在鸟类细胞中复制得更好，而且在哺乳动物的体温较低的情况下。病毒在哺乳动物之间传播或传播给人类之前需要更多的突变。然而，应密切监测哺乳动物物种的感染，以迅速发现可能增加 HPAI H5N1 病毒人畜共患潜力的突变，因为它们可能威胁公共健康。
During the 2020 to 2022 epizootic of highly pathogenic avian influenza virus (HPAI), several infections of mammalian species were reported in Europe. In the Netherlands, HPAI H5N1 virus infections were detected in three wild red foxes (Vulpes vulpes) that were submitted with neurological symptoms between December of 2021 and February of 2022. A histopathological analysis demonstrated that the virus was mainly present in the brain, with limited or no detection in the respiratory tract or other organs. Limited or no virus shedding was observed in throat and rectal swabs. A phylogenetic analysis showed that the three fox viruses were not closely related, but they were related to HPAI H5N1 clade 2.3.4.4b viruses that are found in wild birds. This suggests that the virus was not transmitted between the foxes. A genetic analysis demonstrated the presence of the mammalian adaptation E627K in the polymerase basic two (PB2) protein of the two fox viruses. In both foxes, the avian (PB2-627E) and the mammalian (PB2-627K) variants were present as a mixture in the virus population, which suggests that the mutation emerged in these specific animals. The two variant viruses were isolated, and virus replication and passaging experiments were performed. These experiments showed that the mutation PB2-627K increases the replication of the virus in mammalian cell lines, compared to the chicken cell line, and at the lower temperatures of the mammalian upper respiratory tract. This study showed that the HPAI H5N1 virus is capable of adaptation to mammals; however, more adaptive mutations are required to allow for efficient transmission between mammals. Therefore, surveillance in mammals should be expanded to closely monitor the emergence of zoonotic mutations for pandemic preparedness. IMPORTANCE Highly pathogenic avian influenza (HPAI) viruses caused high mortality among wild birds from 2021 to 2022 in the Netherlands. Recently, three wild foxes were found to be infected with HPAI H5N1 viruses, likely due to the foxes feeding on infected birds. Although HPAI is a respiratory virus, in these foxes, the viruses were mostly detected in the brain. Two viruses isolated from the foxes contained a mutation that is associated with adaptation to mammals. We show that the mutant virus replicates better in mammalian cells than in avian cells and at the lower body temperature of mammals. More mutations are required before viruses can transmit between mammals or can be transmitted to humans. However, infections in mammalian species should be closely monitored to swiftly detect mutations that may increase the zoonotic potential of HPAI H5N1 viruses, as these may threaten public health.
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禽 H5N1 流感病毒聚合酶复合物中哺乳动物适应突变的鉴定。
影响因子：
16.6
作者：
Taft AS;Ozawa M;Fitch A;Depasse JV;Halfmann PJ;Hill-Batorski L;Hatta M;Friedrich TC;Lopes TJ;Maher EA;Ghedin E;Macken CA;Neumann G;Kawaoka Y
通讯作者：
Kawaoka Y
影响因子：
64.5
作者：
Linster M;van Boheemen S;de Graaf M;Schrauwen EJA;Lexmond P;Mänz B;Bestebroer TM;Baumann J;van Riel D;Rimmelzwaan GF;Osterhaus ADME;Matrosovich M;Fouchier RAM;Herfst S
通讯作者：
Herfst S
DOI：
10.1093/bioinformatics/btq224
发表时间：
2010-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Katoh K;Toh H
通讯作者：
Toh H
影响因子：
6.7
作者：
Galloway SE;Reed ML;Russell CJ;Steinhauer DA
通讯作者：
Steinhauer DA
影响因子：
19
作者：
Bouwstra, R. J.;Koch, G.;Bossers, A.
通讯作者：
Bossers, A.