Bordes Luca, Gerhards Nora M, Roose Marit, Venema Sandra, Engelsma Marc, van der Poel Wim H M, Germeraad Evelien A, Beerens Nancy, Vreman Sandra
Wageningen Bioveterinary Research, Lelystad, Netherlands.
J Gen Virol. 2025 Jul;106(7). doi: 10.1099/jgv.0.002124.
A marked increase in the incidence of mortality amongst wild mammals attributed to infection with highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses was observed in Europe in 2021. Neurological signs and high viral antigen levels in the brain of infected wild mammals indicate that the HPAI H5N1 virus causes severe disease in mammals, but serological analysis suggests that infections may be more widespread, implying that some mammals could experience mild disease. The clinical manifestation and transmissibility of HPAI H5N1 clade 2.3.4.4b viruses amongst mammals represent critical risk factors for potential zoonotic transmission to humans. This study examined the pathogenicity, viral tissue tropism and associated pathology of three HPAI H5N1 viruses in ferrets, which are a model for influenza A infection in humans. Ferrets were experimentally infected with an HPAI H5N1 poultry virus (genotype C) and two HPAI H5N1 viruses (genotype BA) isolated from a red fox, one of which carries the zoonotic PB2-E627K mutation. The red fox isolate, but not the poultry isolate, caused high morbidity, viral shedding and mortality in ferrets. Transmission to co-housed ferrets was investigated in a group setting for the virus carrying the PB2-E627K mutation and caused neurological signs accompanied by prominent viral antigen staining in recipient ferrets compared to directly inoculated ferrets. This study shows that HPAI H5N1 clade 2.3.4.4b viruses can infect mammals with varying pathogenicity and that mammal-to-mammal transmission can occur. This increases the zoonotic potential of the virus and highlights the need for enhanced surveillance in wild mammals for early detection of potential zoonotic threats.
2021年在欧洲观察到，感染高致病性禽流感（HPAI）H5N1进化分支2.3.4.4b病毒的野生哺乳动物死亡率显著上升。受感染野生哺乳动物大脑中的神经症状和高病毒抗原水平表明，HPAI H5N1病毒可在哺乳动物中引发严重疾病，但血清学分析表明感染可能更为广泛，这意味着一些哺乳动物可能经历轻度疾病。HPAI H5N1进化分支2.3.4.4b病毒在哺乳动物中的临床表现和传播性是其向人类进行潜在人畜共患病传播的关键风险因素。本研究检测了三种HPAI H5N1病毒在雪貂中的致病性、病毒组织嗜性及相关病理学，雪貂是甲型流感感染人类的模型。雪貂被实验性感染一种HPAI H5N1家禽病毒（C基因型）和两种从赤狐分离出的HPAI H5N1病毒（BA基因型），其中一种携带人畜共患的PB2-E627K突变。赤狐分离株而非家禽分离株在雪貂中引起了高发病率、病毒脱落和死亡。在群体环境中对携带PB2-E627K突变的病毒进行了向同笼雪貂传播的研究，与直接接种的雪貂相比，接受病毒的雪貂出现了神经症状并伴有显著的病毒抗原染色。本研究表明，HPAI H5N1进化分支2.3.4.4b病毒可感染致病性各异的哺乳动物，且可发生哺乳动物之间的传播。这增加了该病毒的人畜共患病潜力，并突出了加强对野生哺乳动物监测以早期发现潜在人畜共患病威胁的必要性。
