Pathogenicity and transmissibility of bovine-derived HPAI H5N1 B3.13 virus in pigs.

Taeyong Kwon, Jessie D Trujillo, Mariano Carossino, Heather M Machkovech, Konner Cool, Eu Lim Lyoo, Gagandeep Singh, Sujan Kafle, Shanmugasundaram Elango, Govindsamy Vediyappan, Wanting Wei, Nicholas Minor, Franco S Matias-Ferreyra, Igor Morozov, Natasha N Gaudreault, Udeni B R Balasuriya, Lisa Hensley, Diego G Diel, Wenjun Ma, Thomas C Friedrich, Juergen A Richt
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Abstract

Since the first emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses in dairy cattle, the virus has continued to spread, reaching 17 states and at least 970 dairy herds in the United States. Subsequently, spillovers of the virus from dairy cattle to humans have been reported. Pigs are an important reservoir in influenza ecology because they serve as a mixing vessel in which novel reassortant viruses with pandemic potential can be generated. Here, we show that oro-respiratory infection of pigs resulted in productive replication of a bovine-derived HPAI H5N1 B3.13 virus. Infectious virus was mainly identified in the lower respiratory tract of principal infected pigs, and sero-conversion was observed in most of the principal pigs at later time points. In one animal, we detected the emergence of a mutation in hemagglutinin (HA) previously associated with increased affinity for "mammalian-type" α2,6-linked sialic acid receptors, but this mutation did not reach consensus levels. Sentinel contact pigs remained sero-negative throughout the study, indicating lack of transmission. The results support that pigs are susceptible to a bovine-derived HPAI H5N1 B3.13 virus, but this virus did not replicate as robustly in pigs as mink-derived HPAI H5N1 and swine-adapted influenza viruses.

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牛源性高致病性H5N1 B3.13病毒在猪中的致病性和传播性。
自首次在奶牛中出现高致病性禽流感H5N1病毒以来,该病毒继续传播,在美国至少波及17个州和至少970头奶牛群。随后,报告了该病毒从奶牛向人类的溢出。猪是流感生态学中一个重要的储存库,因为它们可以作为一个混合容器,在其中可以产生具有大流行潜力的新型重组病毒。本研究表明,猪的口呼吸道感染导致牛源性高致病性H5N1 B3.13病毒的高效复制。感染病毒主要存在于主感染猪的下呼吸道,大部分主感染猪在较晚的时间点均出现血清转化。在一只动物中,我们检测到血凝素(HA)突变的出现,该突变先前与“哺乳动物型”α2,6-链唾液酸受体的亲和力增加有关,但该突变尚未达到共识水平。在整个研究过程中,哨点接触猪的血清呈阴性,表明没有传播。结果支持猪对牛源性高致病性H5N1 B3.13病毒敏感,但该病毒在猪体内的复制不像水貂源性高致病性H5N1和猪适应型流感病毒那样强劲。
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