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Keywords = viral cross-species transmission

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12 pages, 3009 KiB  
Article
Molnupiravir Inhibits Replication of Multiple Alphacoronavirus suis Strains in Feline Cells
by Tomoyoshi Doki, Kazuki Shinohara, Kaito To and Tomomi Takano
Pathogens 2025, 14(8), 787; https://doi.org/10.3390/pathogens14080787 (registering DOI) - 7 Aug 2025
Abstract
The cross-species spillover of coronaviruses is considered a serious public health risk. Feline coronavirus (FCoV), canine coronavirus (CCoV), and transmissible gastroenteritis virus (TGEV) are all classified under Alphacoronavirus suis and infect companion animals and livestock. Due to their frequent contact with humans, these [...] Read more.
The cross-species spillover of coronaviruses is considered a serious public health risk. Feline coronavirus (FCoV), canine coronavirus (CCoV), and transmissible gastroenteritis virus (TGEV) are all classified under Alphacoronavirus suis and infect companion animals and livestock. Due to their frequent contact with humans, these viruses pose a potential risk of future cross-species transmission. Molnupiravir, a prodrug of N4-hydroxycytidine, exhibits potent antiviral activity against SARS-CoV-2, a member of the Betacoronavirus genus, and has been approved for the treatment of COVID-19. Molnupiravir was recently shown to be effective against FCoV, suggesting broad-spectrum antiviral activity across coronavirus lineages. Based on these findings, the present study investigated whether molnupiravir is also effective against CCoV and TGEV, which belong to the same Alphacoronavirus suis species as FCoV. We examined the in vitro antiviral effects of molnupiravir using four viral strains: FCoV-1 and -2, CCoV-2, and TGEV. Molnupiravir inhibited plaque formation, viral antigen expression, the production of infectious viral particles, and viral RNA replication in a dose-dependent manner in all strains. IC50 values for CCoV-2 and TGEV, calculated using a feline-derived cell line (fcwf-4), were significantly lower than those for FCoV, suggesting higher sensitivity to molnupiravir. These results demonstrate that molnupiravir exhibited broad antiviral activity against animal coronaviruses classified under Alphacoronavirus suis, providing a foundation for antiviral strategies to mitigate the future risk of cross-species transmission. Full article
(This article belongs to the Section Viral Pathogens)
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12 pages, 3211 KiB  
Article
CRISPR/Cas12a-Based One-Tube RT-RAA Assay for PoRV Genotyping
by Mingfang Bi, Zunbao Wang, Kaijie Li, Yuhe Ren, Dan Ma and Xiaobing Mo
Int. J. Mol. Sci. 2025, 26(14), 6846; https://doi.org/10.3390/ijms26146846 - 16 Jul 2025
Viewed by 350
Abstract
Porcine rotavirus (PoRV), a primary etiological agent of viral diarrhea in piglets, frequently co-infects with other enteric pathogens, exacerbating disease severity and causing substantial economic losses. Its genetic recombination capability enables cross-species transmission potential, posing public health risks. Globally, twelve G genotypes and [...] Read more.
Porcine rotavirus (PoRV), a primary etiological agent of viral diarrhea in piglets, frequently co-infects with other enteric pathogens, exacerbating disease severity and causing substantial economic losses. Its genetic recombination capability enables cross-species transmission potential, posing public health risks. Globally, twelve G genotypes and thirteen P genotypes have been identified, with G9, G5, G3, and G4 emerging as predominant circulating strains. The limited cross-protective immunity between genotypes compromises vaccine efficacy, necessitating genotype surveillance to guide vaccine development. While conventional molecular assays demonstrate sensitivity, they lack rapid genotyping capacity and face technical limitations. To address this, we developed a novel diagnostic platform integrating reverse transcription recombinase-aided amplification (RT-RAA) with CRISPR–Cas12a. This system employs universal primers for the simultaneous amplification of G4/G5/G9 genotypes in a single reaction, coupled with sequence-specific CRISPR recognition, achieving genotyping within 50 min at 37 °C with 100 copies/μL sensitivity. Clinical validation showed a high concordance with reverse transcription quantitative polymerase chain reaction (RT-qPCR). This advancement provides an efficient tool for rapid viral genotyping, vaccine compatibility evaluation, and optimized epidemic control strategies. Full article
(This article belongs to the Special Issue Protein Design and Engineering in Biochemistry)
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23 pages, 3759 KiB  
Review
Highly Pathogenic Avian Influenza (H5N1) Clade 2.3.4.4b in Cattle: A Rising One Health Concern
by Ivan Camilo Sanchez-Rojas, D. Katterine Bonilla-Aldana, Catherin Lorena Solarte-Jimenez, Jorge Luis Bonilla-Aldana, Jaime David Acosta-España and Alfonso J. Rodriguez-Morales
Animals 2025, 15(13), 1963; https://doi.org/10.3390/ani15131963 - 3 Jul 2025
Viewed by 1036
Abstract
Highly pathogenic avian influenza (HPAI) H5N1, particularly clade 2.3.4.4b, has demonstrated an unprecedented capacity for cross-species transmission, with recent reports confirming its presence in dairy cattle in the United States of America (USA) in 2024. This unexpected spillover challenges traditional understanding of the [...] Read more.
Highly pathogenic avian influenza (HPAI) H5N1, particularly clade 2.3.4.4b, has demonstrated an unprecedented capacity for cross-species transmission, with recent reports confirming its presence in dairy cattle in the United States of America (USA) in 2024. This unexpected spillover challenges traditional understanding of the virus’s host range and raises serious public health and veterinary concerns. Infected cattle presented with clinical signs such as decreased milk production, thickened or discolored milk, respiratory issues, and lethargy. Pathological findings revealed inflammation of the mammary glands and the detection of a virus in nasal secretions and raw milk, suggesting a potential for both intra- and interspecies transmission. While the current risk of human-to-human transmission remains low, the detection of H5N1 in a human exposed to infected cattle highlights the need for heightened surveillance and protective measures. Moreover, the presence of infectious viruses in the food chain, particularly in unpasteurized milk, introduces a new dimension of zoonotic risk. This review synthesizes emerging evidence on the epidemiology, pathology, diagnostic findings, and zoonotic implications of HPAI H5N1 infection in cattle. It also highlights the importance of genomic surveillance, intersectoral collaboration, and One Health approaches in managing this evolving threat. As the virus continues to circulate and adapt across diverse hosts, including wild birds, domestic poultry, and now mammals, the potential for reassortment and emergence of novel strains remains a significant concern. Immediate actions to strengthen biosecurity, monitor viral evolution, and protect both animal and human populations are critical to mitigate the global risk posed by this expanding panzootic. Full article
(This article belongs to the Special Issue Infection Immunity, Diagnosis and Prevention of Avian Influenza)
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28 pages, 854 KiB  
Review
H5N1 Avian Influenza: A Narrative Review of Scientific Advances and Global Policy Challenges
by Alison Simancas-Racines, Claudia Reytor-González, Melannie Toral and Daniel Simancas-Racines
Viruses 2025, 17(7), 927; https://doi.org/10.3390/v17070927 - 29 Jun 2025
Viewed by 857
Abstract
The H5N1 avian influenza virus continues to evolve into genetically diverse and highly pathogenic clades with increased potential for cross-species transmission. Recent scientific advances have included the development of next-generation vaccine platforms, promising antiviral compounds, and more sensitive diagnostic tools, alongside strengthened surveillance [...] Read more.
The H5N1 avian influenza virus continues to evolve into genetically diverse and highly pathogenic clades with increased potential for cross-species transmission. Recent scientific advances have included the development of next-generation vaccine platforms, promising antiviral compounds, and more sensitive diagnostic tools, alongside strengthened surveillance systems in both animals and humans. However, persistent structural challenges hinder global readiness. Vaccine production is heavily concentrated in high-income countries, limiting equitable access during potential pandemics. Economic and logistical barriers complicate the implementation of control strategies such as vaccination, culling, and compensation schemes. Gaps in international coordination, public communication, and standardization of protocols further exacerbate vulnerabilities. Although sustained human-to-human transmission has not been documented, the severity of confirmed infections and the rapid global spread among wildlife and domestic animals underscore the urgent need for robust preparedness. International organizations have called for comprehensive pandemic response plans, enhanced multisectoral collaboration, and investment in targeted research. Priorities include expanding surveillance to asymptomatic animal hosts, evaluating viral shedding and transmission routes, and developing strain-specific and universal vaccines. Strengthening global cooperation and public health infrastructure will be critical to mitigate the growing threat of H5N1 and reduce the risk of a future influenza pandemic. Full article
(This article belongs to the Special Issue Controlling Zoonotic Viral Diseases from One Health Perspective 2025)
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12 pages, 2046 KiB  
Article
The Giant Panda Transferrin Receptor Facilitates Feline Parvovirus Infection to Drive Cross-Species Transmission
by Qigui Yan, Huanyuan Hu, Shan Zhao, Qin Zhao, Rui Wu, Xiaobo Huang, Yiping Wang, Yiping Wen, Yi Zheng, Fei Zhao, Sanjie Cao, Senyan Du and Yifei Lang
Vet. Sci. 2025, 12(7), 602; https://doi.org/10.3390/vetsci12070602 - 20 Jun 2025
Viewed by 489
Abstract
Feline parvovirus (FPV) causes feline panleukopenia, a highly contagious disease in cats, marked by severe leukopenia, biphasic fever, diarrhea, vomiting, and hemorrhagic enteritis. Recently, FPV infection in giant pandas has increased, causing diarrhea and ultimately fatal outcomes, thereby threatening their survival and reproduction. [...] Read more.
Feline parvovirus (FPV) causes feline panleukopenia, a highly contagious disease in cats, marked by severe leukopenia, biphasic fever, diarrhea, vomiting, and hemorrhagic enteritis. Recently, FPV infection in giant pandas has increased, causing diarrhea and ultimately fatal outcomes, thereby threatening their survival and reproduction. Here, we investigated the transmission of FPV in giant pandas and its interaction with cellular receptors using an FPV strain (pFPV-sc) isolated from giant panda feces. Recombinant feline transferrin receptor 1 (fTfR1) and the giant panda ortholog (gpTfR1) were expressed in non-susceptible HEK293T and HeLa cells, while viral infection levels were measured to determine the effect of gpTfR1 on pFPV-sc replication. The findings indicated that gpTfR1 overexpression in non-susceptible cells significantly enhanced pFPV-sc replication, particularly influencing the viral attachment and internalization stages. Our data further revealed early-stage colocalization between gpTfR1 expression and virus infection, suggesting that gpTfR1 facilitates early viral infection and replication. Taken together, our study provides the first evidence on the mechanism of FPV cross-species infection in giant pandas and elucidates the interaction between gpTfR1 and FPV, which establishes a theoretical basis for the development of preventive and therapeutic strategies, thereby safeguarding the health and survival of giant panda populations from FPV. Full article
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21 pages, 2702 KiB  
Article
Avian Influenza Virus: Comparative Evolution as the Key for Predicting Host Tropism Expansion
by Matteo Mellace, Carlotta Ceniti, Marielda Cataldi, Luca Borrelli and Bruno Tilocca
Pathogens 2025, 14(7), 608; https://doi.org/10.3390/pathogens14070608 - 20 Jun 2025
Viewed by 819
Abstract
The avian influenza virus poses an emerging public health risk due to its ability to cross the species barrier and infect a broad spectrum of hosts, including humans. The aim of this study was to investigate the molecular mechanisms and evolutionary dynamics underlying [...] Read more.
The avian influenza virus poses an emerging public health risk due to its ability to cross the species barrier and infect a broad spectrum of hosts, including humans. The aim of this study was to investigate the molecular mechanisms and evolutionary dynamics underlying the spillover, using a bioinformatics approach to viral sequences. Eight viral proteins involved in the process of adaptation to new hosts were selected, and 156 amino acid mutations potentially associated with interspecies transmission were analyzed. The sequences, obtained from the NCBI Virus database, were aligned with the BLASTP1.4.0 tool and compared through phylogenetic analysis. The results show significant evolutionary proximity between human and animal viral strains, and the identification of shared mutations suggests the presence of conserved mechanisms in spillover. The identification of hosts that share mutations with human strains highlights the potential role of these animals as reservoirs or vectors. This study contributes to the understanding of viral adaptation and provides a starting point for targeted preventive strategies, including molecular surveillance and the development of containment and prevention measures. Full article
(This article belongs to the Section Viral Pathogens)
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24 pages, 488 KiB  
Systematic Review
Transmission Pathways of Zoonotic Influenza Viruses and Influencing Factors: A Systematic Review of Recent Findings
by Rebecca Badra, Wenqing Zhang, John S. L. Tam, Richard Webby, Sylvie van der Werf, Sergejs Nikisins, Ann Cullinane, Saad Gharaibeh, Richard Njouom, Malik Peiris, Ghazi Kayali and Jean-Michel Heraud
Viruses 2025, 17(6), 857; https://doi.org/10.3390/v17060857 - 17 Jun 2025
Viewed by 1008
Abstract
Recent outbreaks of zoonotic influenza viruses underscored the need for a deeper understanding of transmission pathways and factors influencing spillover events. Understanding the combined effects of environmental conditions, host interactions, and viral adaptations is essential for effective preparedness and response. The WHO public [...] Read more.
Recent outbreaks of zoonotic influenza viruses underscored the need for a deeper understanding of transmission pathways and factors influencing spillover events. Understanding the combined effects of environmental conditions, host interactions, and viral adaptations is essential for effective preparedness and response. The WHO public health research agenda for influenza, revised in 2017, recommended research to further define the host-to-host transmission pathways of influenza type A viruses. Since 2017, important research has been conducted, and the global health landscape has changed. Therefore, there is a need to review the transmission pathway studies conducted during the last eight years. We conducted a systematic analysis following the PRISMA guidelines on 7490 PubMed records from 2017 to 2024, of which 219 records were retained. This review evaluates research on zoonotic influenza virus transmission among wild and domestic animals and cross-species transmission to humans. By examining pathways, host, environmental, and viral factors, this review identified key findings and research gaps. Research remains limited in critical areas including transmission pathways among diverse animals, role of environmental factors, and zoonotic potential across regions. Addressing these gaps is essential for improving public health strategies. This review highlights the necessity of integrating a One Health approach in addressing zoonotic influenza risks. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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16 pages, 4131 KiB  
Article
Identification, Pathogenicity, and Reverse Genetics System Construction of a Pseudorabies Virus Isolate from Pigs in China
by Mo Zhou, Haiyang Liang, Nannan Nie, Li Zhang, Rui Zhu, Shinuo Cao and Shanyuan Zhu
Vet. Sci. 2025, 12(6), 519; https://doi.org/10.3390/vetsci12060519 - 26 May 2025
Viewed by 533
Abstract
Pseudorabies virus (PRV) is a highly contagious pathogen in swine that can cross species barriers and infect other mammals, including humans. Given the potential for interspecies transmission and its threat to public health, understanding the molecular biology of PRV strains is essential for [...] Read more.
Pseudorabies virus (PRV) is a highly contagious pathogen in swine that can cross species barriers and infect other mammals, including humans. Given the potential for interspecies transmission and its threat to public health, understanding the molecular biology of PRV strains is essential for developing effective control measures and preparing for future pandemics. In this study, a novel PRV strain, PRV-HL-2021, was isolated from an outbreak in Heilongjiang Province, China. The viral genome was used to establish a reverse genetics system based on a fosmid library of the PRV-HL-2021 genome. This system facilitated the creation of recombinant PRV, including one expressing EGFP and another with deletions in the US9, gI, and gE genes. PRV-HL-2021 was found to be highly lethal to mice in vivo. The recombinant PRV strains, such as rPRV-US9-EGFP and rPRV-delgI/gE/US9, exhibited growth characteristics similar to the parental PRV-HL-2021 strain. The isolation and characterization of PRV-HL-2021 contribute to a better understanding of the genetic diversity of PRV strains. The developed reverse genetics system provides valuable tools for investigating viral functions, creating genetically modified PRV strains, and advancing the development of safer vaccines. These findings will enhance strategies for controlling PRV outbreaks and mitigating its impact on both animal and public health. Full article
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20 pages, 5652 KiB  
Systematic Review
Highly Pathogenic Avian Influenza H5N1 in Cats (Felis catus): A Systematic Review and Meta-Analysis
by D. Katterine Bonilla-Aldana, Jorge Luis Bonilla-Aldana, Jaime David Acosta-España and Alfonso J. Rodriguez-Morales
Animals 2025, 15(10), 1441; https://doi.org/10.3390/ani15101441 - 16 May 2025
Cited by 2 | Viewed by 1458
Abstract
Introduction: Highly pathogenic avian influenza (HPAI) H5N1, a zoonotic virus primarily affecting birds, has shown increasing cross-species transmission, including to domestic animals such as cats. Recent reports of cat infections, often associated with contact with infected birds or the consumption of raw milk [...] Read more.
Introduction: Highly pathogenic avian influenza (HPAI) H5N1, a zoonotic virus primarily affecting birds, has shown increasing cross-species transmission, including to domestic animals such as cats. Recent reports of cat infections, often associated with contact with infected birds or the consumption of raw milk from H5N1-positive cattle, raise concerns about their role in viral adaptation and zoonotic transmission. Objective: To assess the global prevalence and characteristics of H5N1 infections in cats (Felis catus) through a systematic review and meta-analysis. Methods: Following PRISMA guidelines, we conducted a systematic search across PubMed, Scopus, and Web of Science up to 1 March 2025. Observational studies reporting the prevalence or seroprevalence of H5N1 in cats (Felis catus) were included. Data extraction and quality assessment were performed independently by four reviewers. Meta-analyses were conducted using a random-effects model, and heterogeneity was assessed via I2 statistics. Results: Twenty-one studies met the inclusion criteria, of which eight were included in the meta-analysis (n = 3586 cats). The pooled global prevalence of Felis catus infections due to H5N1 influenza was 0.7% (95%CI: 0.3–1.1%), with high heterogeneity (I2 = 86.5%). The prevalence varied by the diagnostic method, region, cat type, and time. Domestic cats and those in Africa had higher infection rates (20.0% and 32.0%, respectively). Case reports (n = 35) revealed a high mortality (74%), predominantly from clade 2.3.4.4b, with neurological and respiratory manifestations. Conclusions: Although the overall prevalence is low, H5N1 infection in cats is increasing, particularly in clade 2.3.4.4b. Their close contact with humans and other animals highlights the need for enhanced surveillance, diagnostics, and One Health strategies to mitigate zoonotic risks. Full article
(This article belongs to the Special Issue Infection Immunity, Diagnosis and Prevention of Avian Influenza)
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16 pages, 1706 KiB  
Review
A Review of Cross-Species Transmission Mechanisms of Influenza Viruses
by Xianfeng Hui, Xiaowei Tian, Shihuan Ding, Ge Gao, Jiyan Cui, Chengguang Zhang, Tiesuo Zhao, Liangwei Duan and Hui Wang
Vet. Sci. 2025, 12(5), 447; https://doi.org/10.3390/vetsci12050447 - 7 May 2025
Viewed by 1712
Abstract
The cross-species transmission of influenza viruses represents a critical link in the pandemic of zoonotic diseases. This mechanism involves multi-level interactions, including viral genetic adaptability, host–receptor compatibility, and ecological drivers. Recent studies have highlighted the essential role of mutations in hemagglutinin and neuraminidase [...] Read more.
The cross-species transmission of influenza viruses represents a critical link in the pandemic of zoonotic diseases. This mechanism involves multi-level interactions, including viral genetic adaptability, host–receptor compatibility, and ecological drivers. Recent studies have highlighted the essential role of mutations in hemagglutinin and neuraminidase in overcoming host barriers, while elucidating the differences in the distribution of host sialic acid receptors. Furthermore, the “mixer” function of intermediate hosts, such as pigs, plays a significant role in viral redistribution. Advances in high-throughput sequencing and structural biology technologies have gradually resolved key molecular markers and host restriction factors associated with these viruses. However, challenges remain in understanding the dynamic evolutionary patterns of virus–host interaction networks, developing real-time early warning capabilities for cross-species transmission, and formulating broad-spectrum prevention and control strategies. Moving forward, it is essential to integrate multidisciplinary approaches to establish a multi-level defense system, leveraging the ‘One Health’ monitoring network, artificial intelligence prediction models, and new vaccine research and development to address the ongoing threat of cross-species transmission of influenza viruses. This paper systematically reviews the research progress and discusses bottlenecks in this field, providing a theoretical foundation for optimizing future prevention and control strategies. Full article
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13 pages, 6349 KiB  
Article
Isolation and Characterization of a Porcine Getah Virus Strain from Sichuan Province
by Lina Shao, Mincai Nie, Baoling Liu, Fengqin Li, Tong Xu, Lei Xu, Lishuang Deng, Hanyu Li, Lei Zhao, Youyou Li, Leyi Zhang, Yixin Yan, Zhiwen Xu and Ling Zhu
Vet. Sci. 2025, 12(3), 276; https://doi.org/10.3390/vetsci12030276 - 15 Mar 2025
Viewed by 973
Abstract
Following its initial documented emergence in Hunan’s swine facilities in 2017, GETV has inflicted considerable financial damage upon China’s pork production sector. Beyond its impact on swine, GETV also poses a potential risk to other animal species and public health, primarily due to [...] Read more.
Following its initial documented emergence in Hunan’s swine facilities in 2017, GETV has inflicted considerable financial damage upon China’s pork production sector. Beyond its impact on swine, GETV also poses a potential risk to other animal species and public health, primarily due to its mosquito-borne transmission. Between September 2020 and May 2021, a GETV outbreak occurred on a commercial swine farm in Sichuan Province, where affected animals exhibited movement disorders, neurological symptoms, and mild diarrhea, with severe cases resulting in mortality. To elucidate the genetic characteristics and transmission dynamics of the virus, a comprehensive investigation of this outbreak was conducted. Clinical samples from diseased or deceased swine were collected and analyzed by PCR, confirming the presence of GETV infection. Additionally, differential diagnostic assays were performed for other common swine pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV), pseudorabies virus (PRV), classical swine fever virus (CSFV), and atypical porcine pestivirus (APPV). All tests yielded negative results, confirming GETV as the sole etiological agent of the outbreak. The GETV-positive samples were inoculated into BHK-21 cells, leading to the isolation of a GETV strain (SC202009). Whole-genome sequence analysis revealed that SC202009 belongs to the GIII genotype of GETV, with a nucleotide sequence identity ranging from 95.1% to 99.8% compared to reference sequences in GenBank. This high level of sequence identity suggests that SC202009 is closely related to other circulating strains in the region, indicating potential local transmission networks and endemic viral circulation. The nucleotide sequence identity of the E2 gene ranged from 94.2% to 99.6%, while the E2 protein amino acid sequence identity ranged from 97.2% to 99.5%. Phylogenetic analysis further indicated that SC202009 is genetically distant from the original Malaysian prototype strain (MM2021) but shares high sequence identity with several strains isolated in Sichuan Province, including SC266, SC201807, and SC483. Notably, NMJA_F2_18-8L-NH-Cxp-Y-1-1 was isolated from Culex pipiens, suggesting a mosquito-borne transmission route. These findings provide novel insights into the regional dissemination patterns and genetic diversity of GETV in China. These results also highlight the importance of the continuous surveillance of viral genetic variations and the elucidation of transmission dynamics to develop effective control strategies and mitigate potential public health risks. Future studies should focus on the ecological and environmental factors influencing GETV transmission, particularly the role of mosquito vectors in cross-species viral spread, to enhance targeted prevention and control measures for this emerging arboviral threat. Full article
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15 pages, 538 KiB  
Review
Comprehensive Insights into Highly Pathogenic Avian Influenza H5N1 in Dairy Cattle: Transmission Dynamics, Milk-Borne Risks, Public Health Implications, Biosecurity Recommendations, and One Health Strategies for Outbreak Control
by Henrietta Owusu and Yasser M. Sanad
Pathogens 2025, 14(3), 278; https://doi.org/10.3390/pathogens14030278 - 13 Mar 2025
Cited by 4 | Viewed by 3579
Abstract
Highly pathogenic avian influenza (HPAI) H5N1 has been traditionally linked to poultry and wild birds, which has recently become a serious concern for dairy cattle, causing outbreaks all over the United States. The need for improved surveillance, biosecurity protocols, and interagency collaboration is [...] Read more.
Highly pathogenic avian influenza (HPAI) H5N1 has been traditionally linked to poultry and wild birds, which has recently become a serious concern for dairy cattle, causing outbreaks all over the United States. The need for improved surveillance, biosecurity protocols, and interagency collaboration is highlighted by the discovery of H5N1 in dairy herds in several states and its human transmission. The epidemiology, transmission dynamics, and wide-ranging effects of H5N1 in cattle are reviewed in this paper, with particular attention paid to the disease’s effects on agricultural systems, public health, and animal health. Nonspecific clinical symptoms, such as decreased milk production and irregular milk consistency, are indicative of infection in dairy cows. Alarmingly, significant virus loads have been discovered in raw milk, raising worries about potential zoonotic transmission. The dangers of viral spillover between species are further highlighted by cases of domestic cats experiencing severe neurological symptoms after ingesting raw colostrum and milk from infected cows. Even though human cases remain rare, and they are mostly related to occupational exposure, constant attention is required due to the possibility of viral adaptability. The necessity of a One Health approach that integrates environmental, animal, and human health efforts is further supported by the broad occurrence of H5N1 across multiple species. For early detection, containment, and mitigation, cooperation between veterinary clinics, public health organizations, and agricultural stakeholders is crucial. Controlling the outbreak requires stringent movement restrictions, regular testing of dairy cows in reference labs, and adherence to biosecurity procedures. This review highlights the importance of thorough and coordinated efforts to manage H5N1 in dairy cattle by combining existing knowledge and pointing out gaps in surveillance and response strategies. Additionally, it sheds light on the potential risk of consumption of cow’s milk contaminated with H5N1 virus by humans and other companion animals like cats. In the face of this changing threat, proactive monitoring, strict biosecurity protocols, and cross-sector cooperation are crucial for reducing financial losses and protecting human and animal health. Full article
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17 pages, 2448 KiB  
Article
Genetic Diversity and Molecular Evolution of Hepatitis E Virus Within the Genus Chirohepevirus in Bats
by Bo Wang, Peter Cronin, Marcus G. Mah, Xing-Lou Yang and Yvonne C. F. Su
Viruses 2025, 17(3), 339; https://doi.org/10.3390/v17030339 - 28 Feb 2025
Viewed by 922
Abstract
Hepatitis E virus (HEV) is a major zoonotic pathogen causing hepatitis E, with strains identified in various animal species, including pigs, wild boar, rabbits, deer, camels, and rats. These variants are capable of crossing species barriers and infecting humans. HEV belongs to the [...] Read more.
Hepatitis E virus (HEV) is a major zoonotic pathogen causing hepatitis E, with strains identified in various animal species, including pigs, wild boar, rabbits, deer, camels, and rats. These variants are capable of crossing species barriers and infecting humans. HEV belongs to the family Hepeviridae, which has recently divided into two subfamilies: Orthohepevirinae and Parahepevirinae, and five genera: Paslahepevirus, Avihepevirus, Rocahepevirus, Chirohepevirus, and Piscihepevirus. Recent advances in high-throughput sequencing, particularly of bat viromes, have revealed numerous HEV-related viruses, raising concerns about their zoonotic potential. Bat-derived HEVs have been classified into the genus Chirohepevirus, which includes three distinct species. In this study, we analyzed 64 chirohepevirus sequences from 22 bat species across six bat families collected from nine countries. Twelve sequences represent complete or nearly complete viral genomes (>6410 nucleotides) containing the characteristic three HEV open reading frames (ORFs). These strains exhibited high sequence divergence (>25%) within their respective host genera or species. Phylogenetic analyses with maximum likelihood methods identified at least seven distinct subclades within Chirohepevirus, each potentially representing an independent species. Additionally, the close phylogenetic relationship between chirohepevirus strains and their bat hosts indicates a pattern of virus–host co-speciation. Our findings expand the known diversity within the family Hepeviridae and provide new insights into the evolution of bat-associated HEV. Continued surveillance of chirohepevirus will be essential for understanding its potential for zoonotic transmission and public health risks. Full article
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17 pages, 1413 KiB  
Article
Spatial Landscape Structure Influences Cross-Species Transmission in a Rabies-like Virus Model
by Norma Rocio Forero-Muñoz, Gabriel Dansereau, Francois Viard, Emily Acheson, Patrick Leighton and Timothée Poisot
Microorganisms 2025, 13(2), 416; https://doi.org/10.3390/microorganisms13020416 - 14 Feb 2025
Viewed by 1138
Abstract
In this study, we simulated biologically realistic agent-based models over neutral landscapes to examine how spatial structure affects the spread of a rabies-like virus in a two-species system. We built landscapes with varying autocorrelation levels and simulated disease dynamics using different transmission rates [...] Read more.
In this study, we simulated biologically realistic agent-based models over neutral landscapes to examine how spatial structure affects the spread of a rabies-like virus in a two-species system. We built landscapes with varying autocorrelation levels and simulated disease dynamics using different transmission rates for intra- and interspecies spread. The results were analysed based on combinations of spatial landscape structures and transmission rates, focusing on the median number of new reservoir and spillover cases. We found that both spatial landscape structures and viral transmission rates are key factors in determining the number of infected simulated agents and the epidemiological week when the highest number of cases occurs. While isolated habitat patches with elevated carrying capacity pose significant risks for viral transmission, they may also slow the spread compared to more connected patches, depending on the modelled scenario. This study highlights the importance of spatial landscape structure and viral transmission rates in cross-species spread. Our findings have implications for disease control strategies and suggest that future research should also focus on how landscape factors interact with pathogen dynamics, especially in those locations where susceptible agents could be more in contact with pathogens with high transmission rates. Full article
(This article belongs to the Special Issue Rabies Virus: Infections, Reservoirs and Vectors)
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20 pages, 1144 KiB  
Review
Pandemic-Proofing: Intercepting Zoonotic Spillover Events
by Bharti Bhatia, Sudipta Sonar, Seema Khan and Jayanta Bhattacharya
Pathogens 2024, 13(12), 1067; https://doi.org/10.3390/pathogens13121067 - 3 Dec 2024
Cited by 5 | Viewed by 7204
Abstract
Zoonotic spillover events pose a significant and growing threat to global health. By focusing on preventing these cross-species transmissions, we can significantly mitigate pandemic risks. This review aims to analyze the mechanisms of zoonotic spillover events, identify key risk factors, and propose evidence-based [...] Read more.
Zoonotic spillover events pose a significant and growing threat to global health. By focusing on preventing these cross-species transmissions, we can significantly mitigate pandemic risks. This review aims to analyze the mechanisms of zoonotic spillover events, identify key risk factors, and propose evidence-based prevention strategies to reduce future pandemic threats. Through a comprehensive literature review and analysis of major databases including PubMed, Web of Science, and Scopus from 1960–2024, we examined documented spillover events, their outcomes, and intervention strategies. This article emphasizes that targeting the root cause—the spillover event itself—is key to averting future pandemics. By analyzing historical and contemporary outbreaks, we extract crucial insights into the dynamics of zoonotic transmission. Factors underlying these events include increased human–animal contact due to habitat encroachment, agricultural intensification, and wildlife trade. Climate change, global travel, and inadequate healthcare infrastructure exacerbate risks. The diversity of potential viral reservoirs and rapid viral evolution present major challenges for prediction and prevention. Solutions include enhancing surveillance of wildlife populations, improving biosecurity measures, investing in diagnostic capabilities, and promoting sustainable wildlife management. A “One Health” approach integrating human, animal, and environmental health is crucial. Predictive modelling, international cooperation, and public education are key strategies. Developing pre-exposure prophylactics and post-exposure treatments is essential for mitigating outbreaks. While obstacles remain, advances in genomics and ecological modelling offer hope. A proactive, comprehensive approach addressing the root causes of spillover events is vital for safeguarding global health against future pandemics. Full article
(This article belongs to the Special Issue One Health and Neglected Zoonotic Diseases)
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