Viral Diseases of Horses and Humans: Epidemiology, Pathogenesis and Immunity

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (20 April 2023) | Viewed by 28253

Special Issue Editors


E-Mail Website1 Website2
Guest Editor
Visiting Research Scientist, Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK
Interests: viral zoonootic diseases; equine viral diseases; SARS-CoV-2; coronaviruses; Ebola; vaccinology; pathogenesis; correlates of protection

E-Mail Website
Guest Editor
ANSES-Animal Health Laboratory, 94700 Maisons-Alfort, France
Interests: African horse sickness; West Nile; equine diseases; diagnosis

Special Issue Information

Dear Colleagues, 

Horses and wild equids, like many other mammalian species, are hosts to many viral pathogens, some of which cause diseases of devastating consequences to equine health as well as to the economy of the regions where these diseases occur, including international trade restrictions. This is the case of African horse sickness virus, which currently compromises the growth of equine farming in Sub-Sarahan Africa and has caused catastrophic outbreaks over the past 100 years in North Africa, Arabia, Middle East, India and lately South-East Asia. Others, such as equine influenza virus, circulate in horse populations periodically and their control represent a continuous economic burden to the equine sports industry. These and other equine viruses circulate in nature between wild-life animal hosts and domestic horses, but there is a paucity of information regarding the biological cycle of these viruses, and important gaps of knowledge remain to be fulfilled in this area. Inter-species transmission of equine viruses is particularly interesting. Many viruses causing disease in equids do so in humans, such is the case of the arboviral encephalitides caused by alphaviruses (Eastern, Western and Venezuelan equine encephalitis viruses), flaviviruses (Japanese encephalitis, West Nile, St. Luis Encephalitis, Usutu, Louping ill, Powassan, Tick-borne encephalitis viruses) and Bunyaviruses (La Crosse, James Town Canyon viruses). The clinical manifestations, pathology and pathogenesis of these diseases in horses share common features to those observed in humans. Also, some of these pathogens have zoonotic potential and in other cases equids and humans act as a dead-end host of the epidemiological cycle of the virus.

Equine virology is a fascinating field and many questions regarding immunology, pathogenesis, host-virus interactions and transmission remain unanswered but progress in our understanding of many of these diseases is constrained by logistical, ethical and financial difficulties derived from working in the target species. Despite these difficulties, important advances have been made in the field in the last 20 years.

In this Special Issue, we invite colleagues to submit original research articles and scientific reviews on the immuno-biology, pathogenesis, epidemiology and transmission of equine viral diseases that have an impact beyond veterinary medicine.

Dr. Javier Castillo-Olivares
Dr. Stephan Zientara
Guest Editors

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Keywords

  • equine viruses
  • emerging
  • transboundary
  • pathogenesis
  • immunology
  • vaccines
  • encephalitis

Published Papers (11 papers)

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Research

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19 pages, 2645 KiB  
Article
Investigating the Role of African Horse Sickness Virus VP7 Protein Crystalline Particles on Virus Replication and Release
by Shani Bekker, Christiaan A. Potgieter, Vida van Staden and Jacques Theron
Viruses 2022, 14(10), 2193; https://doi.org/10.3390/v14102193 - 04 Oct 2022
Viewed by 1486
Abstract
African horse sickness is a deadly and highly infectious disease of equids, caused by African horse sickness virus (AHSV). AHSV is one of the most economically important members of the Orbivirus genus. AHSV is transmitted by the biting midge, Culicoides, and therefore [...] Read more.
African horse sickness is a deadly and highly infectious disease of equids, caused by African horse sickness virus (AHSV). AHSV is one of the most economically important members of the Orbivirus genus. AHSV is transmitted by the biting midge, Culicoides, and therefore replicates in both insect and mammalian cell types. Structural protein VP7 is a highly conserved major core protein of orbiviruses. Unlike any other orbivirus VP7, AHSV VP7 is highly insoluble and forms flat hexagonal crystalline particles of unknown function in AHSV-infected cells and when expressed in mammalian or insect cells. To examine the role of AHSV VP7 in virus replication, a plasmid-based reverse genetics system was used to generate a recombinant AHSV that does not form crystalline particles. We characterised the role of VP7 crystalline particle formation in AHSV replication in vitro and found that soluble VP7 interacted with viral proteins VP2 and NS2 similarly to wild-type VP7 during infection. Interestingly, soluble VP7 was found to form uncharacteristic tubule-like structures in infected cells which were confirmed to be as a result of unique VP7-NS1 colocalisation. Furthermore, it was found that VP7 crystalline particles play a role in AHSV release and yield. This work provides insight into the role of VP7 aggregation in AHSV cellular pathogenesis and contributes toward the understanding of the possible effects of viral protein aggregation in other human virus-borne diseases. Full article
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15 pages, 2721 KiB  
Article
Exploiting V-Gene Bias for Rapid, High-Throughput Monoclonal Antibody Isolation from Horses
by Constantinos Kurt Wibmer and Poppy Mashilo
Viruses 2022, 14(10), 2172; https://doi.org/10.3390/v14102172 - 30 Sep 2022
Viewed by 1556
Abstract
Horses and humans share a close relationship that includes both species’ viromes. Many emerging infectious diseases can be transmitted between horses and humans and can exhibit mortality rates as high as 90% in both populations. Antibody biologics represents an emerging field of rapidly [...] Read more.
Horses and humans share a close relationship that includes both species’ viromes. Many emerging infectious diseases can be transmitted between horses and humans and can exhibit mortality rates as high as 90% in both populations. Antibody biologics represents an emerging field of rapidly discoverable and potent antiviral therapeutics. These biologics can be used to provide passive immunity, as well as blueprints for the rational design of novel active vaccine antigens. Here, we exploit the limited diversity of immunoglobulin variable genes used by horses to develop a rapid, high-throughput monoclonal antibody discovery pipeline. The antibodies isolated from two horses in this study were developed with near exclusivity from a few highly related germline genes within a single IgHV and IgλV gene family and could be recovered for cloning with just three primer pairs. This variable gene pairing was compatible with both horse and human immunoglobulin G isotypes, confirming the suitability of an equine antibody discovery pipeline for developing novel therapeutics to meet the One Health approach to infectious diseases. Full article
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13 pages, 590 KiB  
Article
Equus caballus Papillomavirus Type-9 (EcPV9): First Detection in Asymptomatic Italian Horses
by Livia De Paolis, Chiara Grazia De Ciucis, Simone Peletto, Katia Cappelli, Samanta Mecocci, Tiziana Nervo, Lisa Guardone, Maria Ines Crescio, Daniele Pietrucci, Floriana Fruscione, Federica Gabbianelli, Silvia Turco, Katia Varello, Gian Guido Donato, Cristiana Maurella, Paola Modesto, Maria Grazia Maniaci, Giovanni Chillemi, Alessandro Ghelardi and Elisabetta Razzuoli
Viruses 2022, 14(9), 2050; https://doi.org/10.3390/v14092050 - 15 Sep 2022
Cited by 3 | Viewed by 1813
Abstract
Papillomavirus (PV) infections may be related to anogenital lesions and cancer development in humans and several other animal species. To date, 11 different PVs have been reported in horses. Among them, a newly described PV named Equus caballus Papillomavirus Type9 (EcPV9) was thus [...] Read more.
Papillomavirus (PV) infections may be related to anogenital lesions and cancer development in humans and several other animal species. To date, 11 different PVs have been reported in horses. Among them, a newly described PV named Equus caballus Papillomavirus Type9 (EcPV9) was thus far only reported in the semen of a stallion with penile lesions in Australia. This study reports for the first time the presence of EcPV9 in asymptomatic Italian horses. From July 2020 to January 2022, genital brush samples were collected from 209 horses with no apparent signs of neoplastic disease and no PV-associated lesions, clinically examined at the Didactic Veterinary University Hospital (OVUD) of Perugia and at the Veterinary University Hospital (OVU) of Turin. Brushes were submitted to real-time PCR targeting the EcPV9-L1 region. The first amplification targeted a region of ~116 bp, followed by the amplification and sequencing of ~533 bp of the positive samples. EcPV9-L1 DNA was found in eleven horses (5.3%), all female and mainly English Thoroughbred. Co-infection with EcPV2-L1 was found in 7 out of the 11 EcPV9-L1 positive horses (63.6%). This study contributes to the description of the prevalence of exposure or infection of EcPVs in the horse population in Italy, for which data are still limited. In this regard, here we provide a phylogenetic analysis and the completely reconstructed viral genomes of two Italian EcPV type 9 isolates, as well as four EcPV type 2 obtained from co-infected animals. Full article
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22 pages, 3359 KiB  
Article
Generation of a Soluble African Horse Sickness Virus VP7 Protein Capable of Forming Core-like Particles
by Shani Bekker, Henk Huismans and Vida van Staden
Viruses 2022, 14(8), 1624; https://doi.org/10.3390/v14081624 - 26 Jul 2022
Cited by 1 | Viewed by 1458
Abstract
A unique characteristic of the African horse sickness virus (AHSV) major core protein VP7 is that it is highly insoluble, and spontaneously forms crystalline particles in AHSV-infected cells and when expressed in vitro. The aggregation of AHSV VP7 into these crystals presents many [...] Read more.
A unique characteristic of the African horse sickness virus (AHSV) major core protein VP7 is that it is highly insoluble, and spontaneously forms crystalline particles in AHSV-infected cells and when expressed in vitro. The aggregation of AHSV VP7 into these crystals presents many problems in AHSV vaccine development, and it is unclear whether VP7 aggregation affects AHSV assembly or contributes to AHSV pathogenesis. Here, we set out to abolish VP7 self-assembly by targeting candidate amino acid regions on the surface of the VP7 trimer via site-directed mutagenesis. It was found that the substitution of seven amino acids resulted in the complete disruption of AHSV VP7 self-assembly, which abolished the formation of VP7 crystalline particles and converted VP7 to a fully soluble protein still capable of interacting with VP3 to form core-like particles. This work provides further insight into the formation of AHSV VP7 crystalline particles and the successful development of AHSV vaccines. It also paves the way for future research by drawing comparisons with similar viral phenomena observed in human virology. Full article
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17 pages, 9020 KiB  
Communication
Nipah Virus Infection Generates Ordered Structures in Cellulo
by Cecilia Alejandra Vázquez, Lina Widerspick, Roland Thuenauer, Carola Schneider, Rudolph Reimer, Pedro Neira, Catherine Olal, Michelle Heung, Linda Niemetz, Philip Lawrence, Indre Kucinskaite-Kodze, Lars Redecke and Beatriz Escudero-Pérez
Viruses 2022, 14(7), 1523; https://doi.org/10.3390/v14071523 - 12 Jul 2022
Cited by 2 | Viewed by 2642
Abstract
Nipah virus (NiV) is a zoonotic paramyxovirus with a fatality rate of up to 92% in humans. While several pathogenic mechanisms used by NiV to counteract host immune defense responses have been described, all of the processes that take place in cells during [...] Read more.
Nipah virus (NiV) is a zoonotic paramyxovirus with a fatality rate of up to 92% in humans. While several pathogenic mechanisms used by NiV to counteract host immune defense responses have been described, all of the processes that take place in cells during infection are not fully characterized. Here, we describe the formation of ordered intracellular structures during NiV infection. We observed that these structures are formed specifically during NiV infection, but not with other viruses from the same Mononegavirales order (namely Ebola virus) or from other orders such as Bunyavirales (Junín virus). We also determined the kinetics of the appearance of these structures and their cellular localization at the cellular periphery. Finally, we confirmed the presence of these NiV-specific ordered structures using structured illumination microscopy (SIM), as well as their localization by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and correlative light and electron microscopy (CLEM). Herein, we describe a cytopathogenic mechanism that provides a new insight into NiV biology. These newly described ordered structures could provide a target for novel antiviral approaches. Full article
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27 pages, 6514 KiB  
Article
An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation
by Marcha Badenhorst, Armin Saalmüller, Janet M. Daly, Reinhard Ertl, Maria Stadler, Christina Puff, Madeleine de le Roi, Wolfgang Baumgärtner, Michael Engelmann, Sabine Brandner, Hannah K. Junge, Barbara Pratscher, Asisa Volz, Bertrand Saunier, Thomas Krey, Johannes Wittmann, Steffen Heelemann, Julien Delarocque, Bettina Wagner, Daniel Todt, Eike Steinmann and Jessika-M. V. Cavalleriadd Show full author list remove Hide full author list
Viruses 2022, 14(7), 1401; https://doi.org/10.3390/v14071401 - 27 Jun 2022
Viewed by 2325
Abstract
Equine hepacivirus (EqHV) is the closest known genetic homologue of hepatitis C virus. An effective prophylactic vaccine is currently not available for either of these hepaciviruses. The equine as potential surrogate model for hepacivirus vaccine studies was investigated, while equine host responses following [...] Read more.
Equine hepacivirus (EqHV) is the closest known genetic homologue of hepatitis C virus. An effective prophylactic vaccine is currently not available for either of these hepaciviruses. The equine as potential surrogate model for hepacivirus vaccine studies was investigated, while equine host responses following vaccination with EqHV E2 recombinant protein and subsequent EqHV inoculation were elucidated. Four ponies received prime and booster vaccinations (recombinant protein, adjuvant) four weeks apart (day −55 and −27). Two control ponies received adjuvant only. Ponies were inoculated with EqHV RNA-positive plasma on day 0. Blood samples and liver biopsies were collected over 26 weeks (day −70 to +112). Serum analyses included detection of EqHV RNA, isotypes of E2-specific immunoglobulin G (IgG), nonstructural protein 3-specific IgG, haematology, serum biochemistry, and metabolomics. Liver tissue analyses included EqHV RNA detection, RNA sequencing, histopathology, immunohistochemistry, and fluorescent in situ hybridization. Al-though vaccination did not result in complete protective immunity against experimental EqHV inoculation, the majority of vaccinated ponies cleared the serum EqHV RNA earlier than the control ponies. The majority of vaccinated ponies appeared to recover from the EqHV-associated liver insult earlier than the control ponies. The equine model shows promise as a surrogate model for future hepacivirus vaccine research. Full article
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14 pages, 3140 KiB  
Article
Inactivation Methods for Experimental Nipah Virus Infection
by Lina Widerspick, Cecilia Alejandra Vázquez, Linda Niemetz, Michelle Heung, Catherine Olal, András Bencsik, Christoph Henkel, Anneke Pfister, Jesús Emanuel Brunetti, Indre Kucinskaite-Kodze, Philip Lawrence, César Muñoz Fontela, Sandra Diederich and Beatriz Escudero-Pérez
Viruses 2022, 14(5), 1052; https://doi.org/10.3390/v14051052 - 15 May 2022
Cited by 5 | Viewed by 2689
Abstract
Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe disease in humans and livestock. Due to its high pathogenicity in humans and the lack of available vaccines and therapeutics, NiV needs to be handled in biosafety level 4 (BSL-4) laboratories. Safe [...] Read more.
Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe disease in humans and livestock. Due to its high pathogenicity in humans and the lack of available vaccines and therapeutics, NiV needs to be handled in biosafety level 4 (BSL-4) laboratories. Safe inactivation of samples containing NiV is thus necessary to allow further processing in lower containment areas. To date, there is only limited information available on NiV inactivation methods validated by BSL-4 facilities that can be used as a reference. Here, we compare some of the most common inactivation methods in order to evaluate their efficacy at inactivating NiV in infected cells, supernatants and organs. Thus, several physical and chemical inactivation methods, and combinations thereof, were assessed. Viral replication was monitored for 3 weeks and NiV presence was assessed by RT-qPCR, plaque assay and indirect immunofluorescence. A total of nineteen methods were shown to reduce NiV infectious particles in cells, supernatants and organs to undetectable levels. Therefore, we provide a list of methods for the safe and efficient inactivation of NiV. Full article
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Review

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31 pages, 2051 KiB  
Review
Equine Rotavirus A under the One Health Lens: Potential Impacts on Public Health
by Mariano Carossino, Maria Aldana Vissani, Maria E. Barrandeguy, Udeni B. R. Balasuriya and Viviana Parreño
Viruses 2024, 16(1), 130; https://doi.org/10.3390/v16010130 - 16 Jan 2024
Cited by 1 | Viewed by 1723
Abstract
Group A rotaviruses are a well-known cause of viral gastroenteritis in infants and children, as well as in many mammalian species and birds, affecting them at a young age. This group of viruses has a double-stranded, segmented RNA genome with high genetic diversity [...] Read more.
Group A rotaviruses are a well-known cause of viral gastroenteritis in infants and children, as well as in many mammalian species and birds, affecting them at a young age. This group of viruses has a double-stranded, segmented RNA genome with high genetic diversity linked to point mutations, recombination, and, importantly, reassortment. While initial molecular investigations undertaken in the 1900s suggested host range restriction among group A rotaviruses based on the fact that different gene segments were distributed among different animal species, recent molecular surveillance and genome constellation genotyping studies conducted by the Rotavirus Classification Working Group (RCWG) have shown that animal rotaviruses serve as a source of diversification of human rotavirus A, highlighting their zoonotic potential. Rotaviruses occurring in various animal species have been linked with contributing genetic material to human rotaviruses, including horses, with the most recent identification of equine-like G3 rotavirus A infecting children. The goal of this article is to review relevant information related to rotavirus structure/genomic organization, epidemiology (with a focus on human and equine rotavirus A), evolution, inter-species transmission, and the potential zoonotic role of equine and other animal rotaviruses. Diagnostics, surveillance and the current status of human and livestock vaccines against RVA are also reviewed. Full article
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22 pages, 3002 KiB  
Review
Comparison of West Nile Virus Disease in Humans and Horses: Exploiting Similarities for Enhancing Syndromic Surveillance
by Erika R. Schwarz and Maureen T. Long
Viruses 2023, 15(6), 1230; https://doi.org/10.3390/v15061230 - 24 May 2023
Cited by 2 | Viewed by 2387
Abstract
West Nile virus (WNV) neuroinvasive disease threatens the health and well-being of horses and humans worldwide. Disease in horses and humans is remarkably similar. The occurrence of WNV disease in these mammalian hosts has geographic overlap with shared macroscale and microscale drivers of [...] Read more.
West Nile virus (WNV) neuroinvasive disease threatens the health and well-being of horses and humans worldwide. Disease in horses and humans is remarkably similar. The occurrence of WNV disease in these mammalian hosts has geographic overlap with shared macroscale and microscale drivers of risk. Importantly, intrahost virus dynamics, the evolution of the antibody response, and clinicopathology are similar. The goal of this review is to provide a comparison of WNV infection in humans and horses and to identify similarities that can be exploited to enhance surveillance methods for the early detection of WNV neuroinvasive disease. Full article
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20 pages, 1173 KiB  
Review
A Review on Equine Influenza from a Human Influenza Perspective
by Fleur Whitlock, Pablo R. Murcia and J. Richard Newton
Viruses 2022, 14(6), 1312; https://doi.org/10.3390/v14061312 - 15 Jun 2022
Cited by 4 | Viewed by 4225
Abstract
Influenza A viruses (IAVs) have a main natural reservoir in wild birds. IAVs are highly contagious, continually evolve, and have a wide host range that includes various mammalian species including horses, pigs, and humans. Furthering our understanding of host-pathogen interactions and cross-species transmissions [...] Read more.
Influenza A viruses (IAVs) have a main natural reservoir in wild birds. IAVs are highly contagious, continually evolve, and have a wide host range that includes various mammalian species including horses, pigs, and humans. Furthering our understanding of host-pathogen interactions and cross-species transmissions is therefore essential. This review focuses on what is known regarding equine influenza virus (EIV) virology, pathogenesis, immune responses, clinical aspects, epidemiology (including factors contributing to local, national, and international transmission), surveillance, and preventive measures such as vaccines. We compare EIV and human influenza viruses and discuss parallels that can be drawn between them. We highlight differences in evolutionary rates between EIV and human IAVs, their impact on antigenic drift, and vaccine strain updates. We also describe the approaches used for the control of equine influenza (EI), which originated from those used in the human field, including surveillance networks and virological analysis methods. Finally, as vaccination in both species remains the cornerstone of disease mitigation, vaccine technologies and vaccination strategies against influenza in horses and humans are compared and discussed. Full article
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43 pages, 3752 KiB  
Review
Henipavirus Immune Evasion and Pathogenesis Mechanisms: Lessons Learnt from Natural Infection and Animal Models
by Philip Lawrence and Beatriz Escudero-Pérez
Viruses 2022, 14(5), 936; https://doi.org/10.3390/v14050936 - 29 Apr 2022
Cited by 9 | Viewed by 4092
Abstract
Nipah henipavirus (NiV) and Hendra henipavirus (HeV) are zoonotic emerging paramyxoviruses causing severe disease outbreaks in humans and livestock, mostly in Australia, India, Malaysia, Singapore and Bangladesh. Both are bat-borne viruses and in humans, their mortality rates can reach 60% in the case [...] Read more.
Nipah henipavirus (NiV) and Hendra henipavirus (HeV) are zoonotic emerging paramyxoviruses causing severe disease outbreaks in humans and livestock, mostly in Australia, India, Malaysia, Singapore and Bangladesh. Both are bat-borne viruses and in humans, their mortality rates can reach 60% in the case of HeV and 92% for NiV, thus being two of the deadliest viruses known for humans. Several factors, including a large cellular tropism and a wide zoonotic potential, con-tribute to their high pathogenicity. This review provides an overview of HeV and NiV pathogenicity mechanisms and provides a summary of their interactions with the immune systems of their different host species, including their natural hosts bats, spillover-hosts pigs, horses, and humans, as well as in experimental animal models. A better understanding of the interactions between henipaviruses and their hosts could facilitate the development of new therapeutic strategies and vaccine measures against these re-emerging viruses. Full article
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