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Siepker, C.

Publications and source records attributed to Siepker, C..

4 recordsLinked to original sources

Comparative Distribution of α2,3- and α2,6-Linked Sialic Acid Receptors and Influenza A(H5N1) Virus Binding in Sheep, Goats, and Alpacas

Highly pathogenic avian influenza virus (HPAIV) H5N1 continues to pose a significant threat to animal and human health. Since 2022, an expanded host range has been observed, as illustrated by the H5N1 outbreak in dairy cows. Other minor livestock species, such as sheep, goats, and alpacas, have also tested positive for H5N1 for the first time, raising concerns about its impact on previously overlooked livestock species. In this study, we first characterized the distribution of sialic acid (SA) receptors across respiratory and non-respiratory tissues of sheep, goats, and alpacas using Maackia amurensis (SA 2,3) and Sambucus nigra (SA 2,6) lectins. We found that both SA receptors are present in all tissues across species, with notable differences in their distribution and abundance. Next, we developed recombinant LPAIV H5N1 viruses over a laboratory-adapted backbone to evaluate tissue-specific virus binding profiles. The results show that a representative H5N1 virus from clade 2.3.4.4b binds effectively to respiratory and non-respiratory tissues across all species. The strongest virus binding was observed in sheep, followed by goats and, lastly, alpacas. Similar binding patterns were observed with an LPAIV version of clade 2.3.4.4b and a Gs/Gd lineage precursor prototype virus. Finally, we show that H1N1 and H3N2 viruses also bind to respiratory tissues of sheep and goats. These findings provide important insights into the potential susceptibility of minor livestock species to HPAIV H5N1 and other influenza subtypes. Our results contribute to a better understanding of influenza tissue tropism across livestock species and its potential implications for zoonotic transmission.

microbiology↗

Exploring influenza A virus receptor distribution in the lactating mammary gland of domesticated livestock and in human breast tissue.

The spread of the highly pathogenic avian influenza (HPAI) H5N1 virus among dairy cattle illustrates the adaptability of influenza A viruses (IAV) to infect non-traditional species. While IAV-specific sialic acid (SA) receptors have been identified in the mammary glands of dairy cattle, their presence in pigs, sheep, goats, and alpacas has not been studied until now. The zoonotic transmission of HPAI H5N1 to dairy and poultry farm workers during outbreaks raises public health concerns. This study employed lectin histochemistry to examine the mammary glands of livestock and humans. We found that these tissues were rich in SA 2,6-Gal receptors, followed by SA 2,3-Gal receptors, essential for IAV binding. Notably, the A(H5N1) clade 2.3.4.4b virus could bind to mammary tissue from both cattle and pigs. These findings highlight the potential for HPAI H5N1 to infect and spread within the mammary glands of production animals and humans.

immunology↗

Highly Pathogenic Avian Influenza A (H5N1) clade 2.3.4.4b Virus detected in dairy cattle

The global emergence of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b viruses poses a significant global public health threat. Until March 2024, no outbreaks of this virus clade had occurred in domestic cattle. We genetically characterize HPAI viruses from dairy cattle showing an abrupt drop in milk production. They share nearly identical genome sequences, forming a new genotype B3.13 within the 2.3.4.4b clade. B3.13 viruses underwent two reassortment events since 2023 and exhibit critical mutations in HA, M1, and NS genes but lack critical mutations in PB2 and PB1 genes, which enhance virulence or adaptation to mammals. The PB2 E627K mutation in a human case underscores the potential for rapid evolution post-infection, highlighting the need for continued surveillance to monitor public health threats.

microbiology↗

Randomly primed, strand-switching MinION-based sequencing for the detection and characterization of cultured RNA viruses

RNA viruses rapidly mutate, which can result in increased virulence, increased escape from vaccine protection, and false negative detection results. Targeted detection methods have a limited ability to detect unknown viruses and often provide insufficient data to detect coinfections or identify antigenic variants. Random, deep sequencing is a method that can more fully detect and characterize RNA viruses and is often coupled with molecular techniques or culture methods for viral enrichment. Viral culture coupled with third-generation sequencing were tested for the ability to detect and characterize RNA viruses. Cultures of bovine viral diarrhea virus, canine distemper virus, epizootic hemorrhagic disease virus, infectious bronchitis virus, two influenza A viruses, and porcine respiratory and reproductive syndrome virus were sequenced on the MinION platform using a random, reverse primer in a strand-switching reaction, coupled with PCR-based barcoding. Reads were taxonomically classified and used for reference-based sequence building using a stock personal computer. This method accurately detected and identified complete coding sequence genomes with a minimum of 20x coverage depth for all seven viruses, including a sample containing two viruses. Each lineage-typing region had at least 26x coverage depth for all viruses. Furthermore, analyzing the canine distemper virus sample through a pipeline devoid of canine distemper virus reference sequences modeled the ability of this protocol to detect unknown viruses. These results show the ability of this technique to detect and characterize dsRNA, negative- and positive-sense ssRNA, nonsegmented, and segmented RNA viruses.

pathology↗