Equid herpesvirus 1 (EHV-1) can cause a wide spectrum of diseases ranging from inapparent respiratory infection to the induction of abortion and, in extreme cases, neurological disease resulting in paralysis and ultimately death. It has been suggested that distinct strains of EHV-1 that differ in pathogenic capacity circulate in the field. In order to investigate this hypothesis, it was necessary to identify genetic markers that allow subgroups of related strains to be identified. We have determined all of the genetic differences between a neuropathogenic strain (Ab4) and a nonneuropathogenic strain (V592) of EHV-1 and developed PCR/ sequencing procedures enabling differentiation of EHV-1 strains circulating in the field. The results indicate the occurrence of several major genetic subgroups of EHV-1 among isolates recovered from outbreaks over the course of 30 years, consistent with the proposal that distinct strains of EHV-1 circulate in the field. Moreover, there is evidence that certain strain groups are geographically restricted, being recovered predominantly from outbreaks occurring in either North America or Europe. Significantly, variation of a single amino acid of the DNA polymerase is strongly associated with neurological versus nonneurological disease outbreaks. Strikingly, this variant amino acid occurs at a highly conserved position for herpesvirus DNA polymerases, suggesting an important functional role.Equid herpesvirus 1 (EHV-1), a member of the subfamily Alphaherpesvirinae, is a highly prevalent equine pathogen that can cause a range of clinical signs, from respiratory distress to the induction of abortion, neonatal foal death, and occasionally neurological damage resulting in paralysis (9,14,19,33,37,61). The severity of disease resulting from EHV-1 infection is likely to be influenced by a number of factors, including the age and physical condition of the host; whether the infection is primary, a reinfection, or a reactivation of latent virus; the immune status of the host; and the pathogenic potential of the strain involved. In order to assess the relative importance of EHV-1 strain variation regarding disease outcome, it is necessary to develop methods enabling precise discrimination between genetic subgroups of interrelated strains. Previous studies have utilized DNA restriction fragment length polymorphism (RFLP) to separate field isolates of EHV-1 into subgroups according to characteristic restriction enzyme site changes and the presence of variable numbers of copies of short sequence repeats. These studies demonstrated a relatively low frequency of genetic polymorphism for EHV-1 and suggested that distinct strains of EHV-1 do exist in the field (3,4,8,25,32,41,54,57). However, the relative lack of variation of EHV-1 sequences between strains has resulted in too few RFLP variants to be identified for detailed epidemiological studies. Furthermore, although such analyses may be used for tracing the genetic relatedness of strains, they allow identification only of those genetic changes resul...
SummaryData analysis workflows in many scientific domains have become increasingly complex and flexible. To assess the impact of this flexibility on functional magnetic resonance imaging (fMRI) results, the same dataset was independently analyzed by 70 teams, testing nine ex-ante hypotheses. The flexibility of analytic approaches is exemplified by the fact that no two teams chose identical workflows to analyze the data. This flexibility resulted in sizeable variation in hypothesis test results, even for teams whose statistical maps were highly correlated at intermediate stages of their analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Importantly, meta-analytic approaches that aggregated information across teams yielded significant consensus in activated regions across teams. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset. Our findings show that analytic flexibility can have substantial effects on scientific conclusions, and demonstrate factors related to variability in fMRI. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for multiple analyses of the same data. Potential approaches to mitigate issues related to analytical variability are discussed.
Summary Reasons for performing study: Respiratory disease is important in young Thoroughbred racehorses, but the variation in the rates of occurrence between different ages and training groups has not been characterised. Objectives: To determine the rates of respiratory disease, particularly inflammatory airway disease (IAD), as well as evidence of infection, and their variation between age and group. Methods: Horses were examined monthly in 7 British flat training yards over a 3 year period. IAD was defined as increased mucus in the trachea with increased proportions of neutrophils in tracheal wash samples. Frequencies of disease outcomes were estimated from the data. Results: The prevalence of IAD was 13.8% and the incidence was 8.9 cases/100 horses/month. Rates varied with training and age groups, decreasing in older animals. The prevalence of nasal discharge (ND) was 4.1%. Rates of bacterial isolation were more common than viral infections. The incidence and prevalence of several bacterial species decreased with age. Conclusions: IAD and ND were common in young racehorses, varying significantly between training groups and decreasing with age, consistent with infection playing a role in aetiology. Potential relevance: The high prevalence of IAD in 2‐year‐old horses in Britain suggests that routine endoscopic examination may be helpful in providing early diagnosis and appropriate therapy. The transmission of bacteria and viruses within and between groups of young animals and the role of infection, stable environment and factors inherent to each horse, including their genetic make‐up, in the multifactorial aetiology of the disease all merit further study.
A case control study of foal diarrhoea in the United Kingdom was carried out over a 3-year period. Clostridium perfringens was significantly associated with foal diarrhoea (Odds Ratio (OR) = 3.0), being isolated from 57% of 421 animals with diarrhoea but from only 27% of 223 healthy foals. Also, C. perfringens was significantly associated with fatal diarrhoea (OR = 4.5). About half of diarrhoea with a fatal outcome was attributable to this organism. The other pathogens significantly associated with diarrhoea were rotavirus (OR = 5.6), Cryptosporidium spp. (OR = 3.2) and the nematode Strongyloides westeri, which was significant only when present in large numbers (> 2000 eggs/g of faeces: OR = 6.1). Salmonella spp. (OR = 14.2) and Cryptosporidium spp. (OR = 3.0) were the only other pathogens associated with fatal illness. Overall, C. perfringens, rotavirus, and large numbers of Cryptosporidium spp. or S. westeri were isolated from 80% of foals with diarrhoea. Thermophilic Campylobacter spp., Yersinia enterocolitica, Escherichia coli and other parasites were not associated with diarrhoea. Carriage of C. perfringens, rotavirus and Cryptosporidium spp. was significantly greater in healthy foals in contact with cases of diarrhoea than in foals that were not in contact with diarrhoea (P < 0.05). There were no statistical interactions between any of the pathogens associated with diarrhoea although separate cases from one location often involved more than one pathogen.
Subtype-1 isolates of Equine herpesvirus-1 (EHV-1) from a quadriplegic horse and from an aborted foetus were compared with each other and with a subtype-2 respiratory isolate. All 3 isolates were detected in the epithelium and macrophages of the respiratory tract. Both the paresis and foetal subtype-1 isolates replicated in the epithelium of the ileum and this correlated with the recovery of virus from faeces in vivo. The paresis subtype-1 isolate also had a predelection for vascular endothelial cells, particularly in the nasal mucosa, but also in the lungs, central nervous system, adrenal and thyroid. In the 9 foals inoculated with the paresis isolate two developed hind limb dysfunction, four developed diarrhoea, and one of these 4 died with an intussusception. The differences between these isolates are discussed in relation to other herpesviruses.
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