The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1

Laval, Kathlyn; Poelaert, Katrien C. K.; Cleemput, Jolien Van; Zhao, Jing; Vandekerckhove, Annelies; Gryspeerdt, Annick; Garré, Barbara; Meulen, Karen van der; Baghi, Hossein Bannazadeh; Dubale, Haileleul Negussie; Žarak, Ines; Crombrugge, Eline Van; Nauwynck, Hans

doi:10.3389/fmicb.2021.662686

Cited by 25 publications

(23 citation statements)

References 104 publications

(126 reference statements)

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“…2 Zhaosu Horse Barn in Yili, Zhaosu, China. 3 Center of Animal Disease Control and Prevention, Acheng District, Harbin, Heilongjiang, China. 4 Cisen Pharmaceutical Co., Ltd, Jining, Shandong, China.…”

Section: Abbreviationsmentioning

confidence: 99%

“…Equid herpesvirus 1 (EHV-1), classified within the family Herpesviridae, the subfamily Alphaherpesvirinae and the genus Varicellovirus [1], is one of the most serious viral pathogens of the horse population as it is frequently associated with abortion, respiratory problems as well as both ocular and neurological diseases in horses. As such, it can have a significant impact not only on equine health but also on the overall equine industry around the world [2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Outbreak of neuropathogenic equid herpesvirus 1 causing abortions in Yili horses of Zhaosu, North Xinjiang, China

et al. 2022

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Background EHV-1 is one of the most serious viral pathogens that frequently cause abortion in horses around the world. However, so far, relatively little information is available on EHV-1 infections as they occur in China. In January 2021, during an abortion storm which occurred in Yili horses at the Chinese State Studs of Zhaosu (North Xinjiang, China), 43 out of 800 pregnant mares aborted. Results PCR detection revealed the presence of EHV-1 in all samples as the possible cause of all abortions, although EHV-4, EHV-2 and EHV-5 were also found to circulate in the aborted fetuses. Furthermore, the partial ORF33 sequences of the 43 EHV-1 shared 99.3–100% and 99.0–100% similarity in nucleotide and amino acid sequences respectively. These sequences not only indicated a highly conserved region but also allowed the strains to group into six clusters. In addition, based on the predicted ORF30 nucleotide sequence, it was found that all the strains carried a guanine at the 2254 nucleotide position (aspartic acid at position 752 of the viral DNA polymerase) and were, therefore, identified as neuropathogenic strains. Conclusion This study is the first one that establishes EHV-1 as the cause of abortions in Yili horses, of China. Further characterization of the ORF30 sequences revealed that all the EHV-1 strains from the study carried the neuropathogenic genotype. Totally, neuropathogenic EHV-1 infection in China’s horse population should be concerned although the virus only detected in Yili horse abortions.

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Section: Abbreviationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Outbreak of neuropathogenic equid herpesvirus 1 causing abortions in Yili horses of Zhaosu, North Xinjiang, China

et al. 2022

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“…Then, EHV-1 infects lymphocytes and subsequently reaches the blood circulation [ 3 , 4 ]. The cell-associated viraemia induces a dissemination of the virus to secondary sites of infection, such as the central nervous system (CNS), the uterus or the eye [ 5 ]. Several studies have suggested that EHM is associated with a single-nucleotide polymorphism at position 2254 in the EHV-1 DNA polymerase gene (ORF 30) [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Oral Administration of Valganciclovir Reduces Clinical Signs, Virus Shedding and Cell-Associated Viremia in Ponies Experimentally Infected with the Equid Herpesvirus-1 C2254 Variant

et al. 2022

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Equid alphaherpesvirus-1 (EHV-1) is one of the main pathogens in horses, responsible for respiratory diseases, ocular diseases, abortions, neonatal foal death and neurological complications such as equine herpesvirus myeloencephalopathy (EHM). Current vaccines reduce the excretion and dissemination of the virus and, therefore, the extent of an epizooty. While their efficacy against EHV-1-induced abortion in pregnant mares and the decreased occurrence of an abortion storm in the field have been reported, their potential efficacy against the neurological form of disease remains undocumented. No antiviral treatment against EHV-1 is marketed and recommended to date. This study aimed to measure the protection induced by valganciclovir (VGCV), the prodrug of ganciclovir, in Welsh mountain ponies experimentally infected with an EHV-1 ORF30-C2254 strain. Four ponies were administered VGCV immediately prior to experimental EHV-1 infection, while another four ponies received a placebo. The treatment consisted in 6.5 mg/kg body weight of valganciclovir administered orally three times the first day and twice daily for 13 days. Clinical signs of disease, virus shedding and viraemia were measured for up to 3 weeks. The severity of the cumulative clinical score was significantly reduced in the treated group when compared with the control group. Shedding of infectious EHV-1 was significantly reduced in the treated group when compared with the control group between Day + 1 (D + 1) and D + 12. Viraemia was significantly reduced in the treated group when compared with the control group. Seroconversion was measured in all the ponies included in the study, irrespective of the treatment received. Oral administration of valganciclovir induced no noticeable side effect but reduced clinical signs of disease, infectious virus shedding and viraemia in ponies experimentally infected with the EHV-1 C2254 variant.

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“…EHV-1 is one of the major infectious agents affecting horses worldwide. The virus is responsible for respiratory disorders, abortion, neonatal foal death, and equine herpes myeloencephalopathy [16]. The main portal of EHV-1 entry is the upper respiratory tract.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Toxins from Staphylococcus aureus and Bordetella bronchiseptica Predispose the Horse’s Respiratory Tract to Equine Herpesvirus Type 1 Infection

Crombrugge

Vanbeylen

Cleemput

et al. 2022

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Respiratory disease in horses is caused by a multifactorial complex of infectious agents and environmental factors. An important pathogen in horses is equine herpesvirus type 1 (EHV-1). During co-evolution with this ancient alphaherpesvirus, the horse’s respiratory tract has developed multiple antiviral barriers. However, these barriers can become compromised by environmental threats. Pollens and mycotoxins enhance mucosal susceptibility to EHV-1 by interrupting cell junctions, allowing the virus to reach its basolateral receptor. Whether bacterial toxins also play a role in this impairment has not been studied yet. Here, we evaluated the role of α-hemolysin (Hla) and adenylate cyclase (ACT), toxins derived from the facultative pathogenic bacterium Staphylococcus aureus (S. aureus) and the primary pathogen Bordetella bronchiseptica (B. bronchiseptica), respectively. Equine respiratory mucosal explants were cultured at an air–liquid interface and pretreated with these toxins, prior to EHV-1 inoculation. Morphological analysis of hematoxylin–eosin (HE)-stained sections of the explants revealed a decreased epithelial thickness upon treatment with both toxins. Additionally, the Hla toxin induced detachment of epithelial cells and a partial loss of cilia. These morphological changes were correlated with increased EHV-1 replication in the epithelium, as assessed by immunofluorescent stainings and confocal microscopy. In view of these results, we argue that the ACT and Hla toxins increase the susceptibility of the epithelium to EHV-1 by disrupting the epithelial barrier function. In conclusion, this study is the first to report that bacterial exotoxins increase the horse’s sensitivity to EHV-1 infection. Therefore, we propose that horses suffering from infection by S. aureus or B. bronchiseptica may be more susceptible to EHV-1 infection.

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The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1

Cited by 25 publications

References 104 publications

Outbreak of neuropathogenic equid herpesvirus 1 causing abortions in Yili horses of Zhaosu, North Xinjiang, China

Outbreak of neuropathogenic equid herpesvirus 1 causing abortions in Yili horses of Zhaosu, North Xinjiang, China

Oral Administration of Valganciclovir Reduces Clinical Signs, Virus Shedding and Cell-Associated Viremia in Ponies Experimentally Infected with the Equid Herpesvirus-1 C2254 Variant

Bacterial Toxins from Staphylococcus aureus and Bordetella bronchiseptica Predispose the Horse’s Respiratory Tract to Equine Herpesvirus Type 1 Infection

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