Researchers at Iowa State University have made a remarkable discovery by identifying highly pathogenic avian influenza (HPAI) H5N1 in dairy cattle, marking the first such case in the United States. Their study, Sialic Acid Receptor Specificity in Mammary Gland of Dairy Cattle Infected with Highly Pathogenic Avian Influenza A(H5N1) Virus, found that specific sialic acid receptors in the cows’ respiratory and mammary tissues facilitate virus attachment, indicating a new potential transmission route from birds to cows and subsequently to humans.
This research underscores the critical need for enhanced surveillance and preventive measures to mitigate the risks of a future pandemic. The presence of these receptors in cattle suggests that the virus could mutate and adapt to new hosts, increasing the risk of cross-species transmission. The findings emphasize the importance of understanding virus transmission dynamics across species and improving public health safety protocols. Given the potential for the virus to spread through contaminated milk, the study also highlights the need for strict pasteurization practices and the provision of personal protective equipment for dairy workers to reduce exposure and transmission risks.
Here is the summary of the Article:
Detection of HPAI H5N1 in Dairy Cattle:
– In March 2024, highly pathogenic avian influenza (HPAI) A(H5N1) virus was detected in dairy cattle in the United States for the first time.
– Presence of specific virus receptors on host cells plays a role in susceptibility to HPAI H5N1 infection.
SA Receptor Specificity:
– Little is known about the distribution of sialic acid (SA) receptors in dairy cattle, especially in mammary glands.
– Respiratory and mammary glands of HPAI H5N1–infected dairy cattle are rich in avian influenza virus–specific SA α2,3-gal.
Viral Spread and Host Range:
– HPAI H5N1 outbreaks were reported in commercial and backyard poultry flocks, leading to infections in multiple mammal species, including dairy cattle.
– The introduction of HPAI H5N1 into dairy cattle is believed to be from a wild bird source.
Receptor Availability:
– Influenza A viruses use host sialic acids as receptors for attachment and entry into cells.
– IAVs from avian species preferentially bind to SA receptors with an α2,3-galactose linkage.
SA Receptor Distribution Profiles:
– Various methods, including plant lectin binding affinity, are used to study SA distribution in animal tissues.
– Plant lectins like SNA and MAL-I are used to detect specific SA receptors.
Study on Holstein Dairy Cattle:
– Formalin-fixed tissues from affected dairy cattle were studied to explore the distribution of SA receptors and factors enabling HPAI H5N1 infection.
– The study aims to understand the uncommon mammary gland infection by HPAI H5N1 virus.
Sample Collection:
– Samples from the trachea, lung, mammary gland tissues, and milk of infected cows were used in the study.
– Diagnosis was based on real-time RT-PCR and immunohistochemistry.
Lesion Patterns in Mammary Glands:
– Mammary glands of infected cows showed a multifocal lesion pattern, aiding in the study of viral distribution within the glands.
– This pattern was crucial for understanding potential binding sites for the virus.
Sample Preparation and Cytologic Evaluation:
– Used milk from EDTA tubes for cytologic evaluation by making direct smears onto cytocentrifuged slides.
– Performed cytocentrifugation at 72 g for 10 minutes and stained slides with modified Wright stain.
Characterization of Mammary Tissues:
– Characterized mammary tissues for sialic acids using lectin histochemistry combined with IAV-Np staining.
– Used specific lectins (SNA, MAL-I, MAL-II) and immunostaining with IAV-Np for characterization.
MulticolorImmunofluorescent Staining:
– Conducted multicolorimmunofluorescent staining using cytokeratin, Iba1, and IAV-Np antibody.
– Examined slides using a microscope equipped with a DP23 camera and CellSyns Dimension software.
Respiratory and Mammary Tissue Evaluation:
– Evaluated the distribution of SA α2–3 and SA α2–6 receptors in respiratory and mammary tissues.
– Used fluorescent and chromogenic-based lectin histochemistry for the evaluation.
Detection Methods and Clinicopathologic Findings:
– Selected respiratory and mammary gland samples from 2 dairy cows with HPAI H5N1 virus infections for evaluation.
– Found clinicopathologic manifestations and detection methods consistent with previous reports.
Mammary Lesions and Cytological Assessment:
– Identified moderate mastitis and neutrophilic inflammation in the HPAI H5N1 virus–infected mammary gland.
– Performed cytological assessment revealing inflammation consistent with mastitis.
Lectin Histochemistry Observations:
– Observed labelings of SNA, MAL-I, and MAL-II in different respiratory tissues and cells.
– Noted differences in intensity and distribution of MAL-I and MAL-II labelings in bronchial epithelium.
Labeling Patterns in Respiratory Epithelium:
– MAL-I and MAL-II labeling was observed in bronchial goblet cells and submucosal glandular epithelial cells.
– MAL-I and MAL-II labeling in bronchioles and alveoli showed diffuse patterns.
Lectin Histochemistry Results:
– Lectin histochemistry results within unaffected and affected tissues closely mirrored fluorescent microscopic findings.
– The sensitivity and localization of labeling with chromogenic, lectin-based assays were not as definitive as fluorescent labeling.
IAV-Np Distribution:
– IAV-Np labeling was more widely distributed and intense in the secretory alveolar epithelium than in the ductal epithelium.
– Some intraluminal cells within secretory alveoli and ducts had both intranuclear and cytoplasmic IAV-Np expression.
Receptor Availability:
– The findings suggest that no limitations would exist regarding receptor availability and distribution in the bovine mammary gland for IAVs to bind.
– The mammal-specific SAα2,6-gal in cattle is mainly confined to the subepithelial region of the trachea, occasionally in the goblet cells and subepithelial glands.
Host Range of IAV:
– IAVs have a broad host range involving avian and mammal species.
– The susceptibility of a host to IAV infection is determined by the type of SA receptor present on the host cell surface, along with other host factors.
Importance of Surveillance:
– The presence of HPAI H5N1 virus in dairy cattle highlights the importance of IAV adaptability to other nontraditional species and cross-species transmission.
– This finding reiterates the need for active IAV surveillance efforts in animal species.
SA Expression and Distribution:
– Our study explores the expression and distribution of SAs in the respiratory tract and mammary glands of Holstein dairy cows naturally infected with HPAI H5N1 virus.
– SAs are widely expressed in these tissues with predominant SA α2,3-gal-β (1–3) GalNAc, followed by α2,6-linked SA and SAα2,3-gal-β (1–4) GlcNAc.
IAV’s SA Receptor Preference:
– IAV strains established in mammals exhibit a higher tropism or affinity for α2,6-linked SA receptors, whereas the HPAI H5N1 virus preferentially binds to α2,3-linked SA receptors.
– SAs are also a major component of milk and cattle milk predominantly contain Neu5Gc versus Neu5Ac.
Binding Affinity to Bovine Respiratory Tract:
– The findings suggest that avian IAVs have the potential binding affinity to the bovine respiratory tract.
– Unlike in pigs and humans, the mammal-specific SAα2,6-gal in cattle is mainly confined to the subepithelial region of the trachea.
Viral Localization and Replication:
– Localization of IAVs in mammary gland cells was observed, with potential replication
– Histologic and immunohistochemical evidence suggests viral infection in macrophages
Pathological Impact on Dairy Cattle:
– IAV infections in dairy cattle can lead to systemic inflammatory responses
– Lesions outside the respiratory tract and potential routes of infection warrant further exploration
Virus-Host Interactions:
– Complex interactions between virus and host cell receptors influence infection efficiency
– Changes in receptor-binding activity due to pH variations impact viral infection processes
Human Infections and Spread:
– Sporadic human cases due to prolonged contact with infected birds have been reported
– Understanding the viral mutations and adaptation to various species is essential in public health preparedness
Research Contributions:
– Research on innate and adaptive immune responses to influenza and coronaviral infections is ongoing
– Collaborative efforts in veterinary pathology and virology are crucial for understanding infectious diseases
Acknowledgements:
– Gratitude expressed to contributors in leadership, guidance, and programmatic support
– Financial and programmatic support provided by Iowa State University for the research
References:
– Key references on the highly pathogenic avian influenza infections in dairy cattle and cats
– Public health actions and studies related to H5N1 and H5N8 viruses spread and impact
Emergence and Evolution of H5N1 Bird Flu:
– CDC provides insightful information on the emergence and evolution of H5N1 bird flu.
– The link offers valuable communication resources and an origin infographic.
Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Infections in Wild Terrestrial Mammals:
– Elsmo et al. discuss infections in wild terrestrial mammals in the United States in 2022.
– The study sheds light on the impact of the virus on mammalian populations.
National Wildlife Disease Program: HPAI Detections in Mammals:
– USDA’s Wildlife Services shares insights on HPAI detections in mammals.
– The data aids in understanding the spread and impact of avian influenza in wildlife.
Sialic Acid Species and Influenza A Virus Host Range:
– Suzuki et al. delve into the role of sialic acid species in determining the host range of influenza A viruses.
– Understanding host-virus interactions is crucial for influenza surveillance and control.
Divergent Pathogenesis and Transmission of Highly Pathogenic Avian Influenza A(H5N1) in Swine:
– Arruda et al. present insights into the pathogenesis and transmission of H5N1 in swine.
– The study highlights the need for vigilance against interspecies transmission.
Evolving Complexities of Influenza Virus and Its Receptors:
– Nicholls et al. discuss the evolving complexities of influenza virus and its receptors.
– Insights into virus-receptor interactions are essential for understanding influenza dynamics.
Antigenic Characterization and Pandemic Risk Assessment of North American H1 Influenza A Viruses in Swine:
– Venkatesh et al. analyze the antigenic characteristics of North American H1 influenza A viruses in swine.
– Assessing pandemic risks in animal populations is crucial for public health preparedness.
Avian Flu: Influenza Virus Receptors in the Human Airway:
– Shinya et al. explore influenza virus receptors in the human airway.
– Understanding viral entry mechanisms aids in developing preventive strategies against zoonotic infections.
Lactational Changes in N-glycoloylneuraminic Acid Content:
– Study on changes in the N-glycoloylneuraminic acid content of bovine milk gangliosides.
– Published in BiolChem Hoppe Seyler in 1993.
Expression of Alpha 2,6-linked Sialic Acid Residues:
– Investigation of alpha 2,6-linked sialic acid residues in neoplastic and normal human colonic mucosa.
– Study conducted by Sata et al. and published in Am J Pathol in 1991.
Highly Pathogenic H5N1 Influenza A Virus Spreads in Human Cells:
– Efficient spread of highly pathogenic H5N1 influenza A virus observed in human primary monocyte-derived macrophages and dendritic cells.
– Research published in Front Immunol in 2018.
Early Apoptosis Limits Avian Influenza Virus Replication:
– Study on the limitation of avian influenza virus replication and pro-inflammatory dysregulation through early apoptosis of porcine alveolar macrophages.
– Findings published in Sci Rep in 2015.
Pathology of Influenza Virus Infections:
– Insight into the pathology of influenza virus infections.
– Published in Annu Rev Pathol in 2008.
Systemic Infection of Avian Influenza A Virus H5N1 Subtype in Humans:
– Study on the systemic infection of avian influenza A virus H5N1 subtype in humans.
– Published in Hum Pathol in 2009.
Highly Pathogenic Avian Influenza Virus Infection in Red Foxes:
– Observation of highly pathogenic avian influenza virus (H5N1) infection in red foxes due to feeding infected bird carcasses.
– Published findings in Emerg Infect Dis in 2008.
Encephalitis and Death in Wild Mammals Infected with Highly Pathogenic Avian Influenza A(H5N8) Virus:
– Report on encephalitis and death in wild mammals at a rehabilitation center after infection with highly pathogenic avian influenza A(H5N8) virus in the United Kingdom.
– Published in Emerg Infect Dis in 2021.
Publication Information:
– Original Publication Date: June 11, 2024
– Volume 30, Number 7—July 2024
Author Contact Information:
– Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, 1907 ISU C Dr, VMRI #2, Iowa State University, Ames, IA 50011, USA
– Email: [Author’s Email Address]
Article Details:
– Sialic Acid Receptor Specificity in Mammary Gland of Dairy Cattle Infected with Highly Pathogenic Avian Influenza A(H5N1) Virus
– Emerging Infectious Diseases, 30(7), 1361-1373
