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F Chianini,
S Sisó,
E Ricci,
S L Eaton,
J Finlayson,
Y Pang,
S Hamilton,
P Steele, H W Reid,
C Cantile,
J Sales,
M Jeffrey,
M P Dagleish,
L González
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ABSTRACT: It is well established that the infectious agent of scrapie can replicate in the lymphoreticular system (LRS). However, the effects of removal of LRS target tissues on the pathogenesis of the infection and the accumulation of disease-associated prion protein (PrP(d)) in LRS tissues on specific immune cell subsets are poorly understood aspects. To address these questions 16 ARQ/ARQ sheep were subcutaneously inoculated in the drainage area of the prefemoral lymph node with brain homogenate derived from Suffolk sheep naturally infected with scrapie. Fourteen sheep were then subjected to either early (14-17 days post-inoculation [dpi]) or late (175-201 dpi) lymphadenectomy and culled at preclinical or clinical stages of infection. Neither late nor even early lymphadenectomy prevented infection or had any effect on the accumulation of PrP(d) in the LRS or CNS suggesting a rapid organic dissemination of the infectious agent after inoculation. Lymph nodes from eight scrapie inoculated sheep selected on the basis of the amount of PrP(d) in their LRS tissues (negative, low or high) were examined for six different immune cell markers. The PrP(d) negative lymph nodes from two sheep with no evidence of scrapie infection showed lower numbers of cluster of determination (CD) 21 positive cells than PrP(d) positive nodes, irrespective of their location (hind leg or head). However, quantitative differences in the expression of this marker were not detected when comparing lymph nodes with low and high levels of PrP(d) accumulation, suggesting that proliferation of CD21 positive cells is related to scrapie infection, but not directly linked to the magnitude of PrP(d) accumulation. An additional observation of the study was that sheep that were methionin-threonine at codon 112 of the prion protein gene showed lower attack rates than methionine homozygotes (67% and 100%, respectively) and also generally lower levels of PrP(d) accumulation in the LRS and brain and increased survival times, suggesting an influence of such polymorphism in the susceptibility to scrapie.
Veterinary Immunology and Immunopathology 01/2013; · 2.08 Impact Factor
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D. HAIG,
D. DEANE,
A. PERCIVAL,
N. MYATT,
J. THOMSON,
L. INGLIS,
J. ROTHEL,
HENG-FONG SEOW,
P. WOOD,
H. R. P. MILLER, H. W. REID
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ABSTRACT: Abstract The in vivo dynamics of differentiated cells and interleukin (IL)-lβ, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN)-γ titres in afferent lymph were compared following orf virus reinfection and inactivated virus injection of previously infected sheep. The biphasic lymphoblast and cytokine response in the lymph to virus reinfection is consistent with a response initially to orf virus as recall antigen followed by a response to viral replication. CD4 T cells increased in output over other cell types in the lymph in both groups. A rapid immune/inflammatory response was detected in lymph plasma as an increase in cytokine titres within 24 h of virus reinfection or injection. Lymph cells producing IL-1β and IL-8 appeared prior to those producing GM-CSF in both groups. In spite of variations in the concentration of individual cytokines in lymph following reinfection, both the size of the orf lesion and the time to resolve were similar in all cases.Résumé— Les dynamiques in vivo des cellules différenciées et des taux d'IL-1β, de GM-CSF et d'interferon γ dans la lymphe afférente furent comparés chez des moutons antéricurement infectés après une réinfection par le virus de l'ecthyma contagieux et après injection d'un virus inactivé. La réponse biphasique lymphoblastique et des cytokines à la réinfection virale est compatibles avec une réponse primaire au virus de l'ecthyma contagieux comme antigène mémoire suivie par une réponse secondaire à la réplication virale. Dans les 2 groupes, le nombre de TCD4 est plus élevé que les autres populations cellulaires mises en évidence dans la lymphe. Une réponse de type immune/inflammatoire est révélée dans le plasma par une élévation des taux de cytokines dans les 24 heures qui suivent la réinfection virale ou l'injection de virus inactivé. Les lymphocytes producteurs dTL-1β et d'IL-8 apparaissent avant les lymphocytes producteurs de GM-CSF dans les deux groupes. En dépit des variations de concentration des cytokines individuelles dans le lymphe après reinfection, à la fois la taille des lesions d'ecthyma et les délais de guérison sont identiques dans tous les cas. [Haig, D., Deane, D., Percival, A., Myatt, N., Thomson, J., Inglis, L., Rothel, J., Heng-Fong Seow, Wood, P., Miller, H. R. P., Reid, H. W. The cytokine response of afferent lymph following orf virus reinfection of sheep (Effet sur les cytokines de la lymphe afferente d'une reinfection par les virus de l'ecthyma contagieux chez le mouton.) Veterinary Dermatology 1996; 7: 11–20.]Resumen Se comparó la actividad de células diferenciadas y los titulos de interleuquina (IL)-1β, IL-8, factor de estimulación de colonias de granulocitos y macrófagos (GM-CSF) e interferon (IFN)-y entre reinfecciones por el virus del ectima contagioso e inyección de virus inactivado de ovinos previamente infectados. La respuesta a la reinfección en forma bifásica linfoblástica y de citoquinas en la linfa está de acuerdo con una respuesta inicial al virus del ectima por estimulación antigénica, seguida por una respuesta a la replicación viral. Las células T CD4 aumentaron respecto a otros tipos celulares en la linfa de ambos grupos. Se detectó una respuesta inmune/inflamatoria rápida en el linfa-plasma en forma de aumento de los titulos de citoquinas dentro de las 24 h de reinfección o inyección del virus. Las células linfáticas productoras de IL-1β e IL-8 aparecicron antes que las productoras de GM-CSF en ambos grupos. A pesar de las variaciones en la concentración de citoquinas individuates en la linfa después de la reinfección, tanto el tamaño de la lesión por el virus del ectima contagioso como el tiempo de resolución fueron similares en todos los casos. [Haig, D., Deane, D., Percival, A., Myatt, N., Thomson, J., Inglis, L., Rothel, J., Heng-Fong Seow, Wood, P., Miller, H. R. P., Reid, H. W. The cytokine response of afferent lymph following orf virus reinfection of sheep (Produccion de citoquinas en el ganglio linfatico afferente tras la reinfección por el virus del ectima contagioso.) Veterinary Dermatology 1996; 7: 11–20.]Zusammenfassung— Es wurde die in-vivo-Dynamik der Titer differenzierter Zellen und Interleukin (1L)-1β, IL-8, Granulozytenmakrophagenkolonien-stimulierender Faktor (GM-CSF) und Interferon (IFN)-γ in afferenter Lymphe nach einer Reinfektion mit ORF-Virus und einer Injektion inaktivierten Virusmaterials von früher infizierten Schafen verglichen. Die biphasische Lymphoblasten- und Zytokin-Reaktion in der Lymphe auf die Virusreinfektion stimmte mit einer initialen Reaktion gegenüber ORF-Virus überein, da der Wiederabruf von Antigen von einer Reaktion auf die Virusreplikation gefolgt wird. CD4-T-Zellen vermehrten sich im Output stärker als andere Zelltypen in der Lymphe beider Gruppen. Es wurde eine rasche immunologische/entzündliche Reaktion im Lymphplasma in Form eines Anstieges von Zytokin-Titern innerhalb von 24 Stunden nach Virusreinfektion oder -injektion festgestellt. Lymphatische Zellen, die IL-1β und IL-8 produzieren, erschienen vor dem Auftreten von solchen, die GM-CSF produzieren, in beiden Gruppen. Trotz des Schwankens der Konzentration der individuellen Zytokine in der Lymphe nach Reinfektion, waren sowohl die Größe der ORF-Veränderungen und die Zeit der Heilung ähnlich in alien Fällen. [Haig, D., Deane, D., Percival, A., Myatt, N., Thomson, J., Inglis, L., Rothel, J., Heng-Fong Seow, Wood, P., Miller, H. R. P., Reid, H. W. The cytokine response of afferent lymph following orf virus reinfection of sheep (Die ZytokinReaktion afferenter Lymphe nach einer Reinfektion mit orf-virus beim schaf.) Veterinary Dermatology 1996; 7: 11–20.]
Veterinary Dermatology 06/2008; 7(1):11 - 20. · 1.94 Impact Factor
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Chapter:
Orf
01/2008: pages 297 - 302; , ISBN: 9780470753316
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S L Eaton,
M Rocchi,
L González,
S Hamilton,
J Finlayson,
J Sales,
M Jeffrey,
P J Steele,
M P Dagleish,
S M Rodger, H W Reid,
F Chianini
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ABSTRACT: In order to investigate the relationship between the immune response to scrapie infection and genetic susceptibility to the disease in sheep, immune cell subsets and prion protein (PrP) expression were determined in susceptible and resistant Suffolk sheep in the preclinical phase of infection. At 6 months of age, 12 ARQ/ARQ (susceptible) and nine ARR/ARR (resistant) scrapie-free Suffolk lambs were challenged subcutaneously with scrapie inoculum. Prefemoral lymphadenectomies were carried out at 14 and 180 days post-inoculation (p.i.) and serial bleeds were collected at monthly intervals for up to 1 year p.i. An indirect double-labelling procedure was carried out on peripheral blood mononuclear cells (PBMCs) and lymph node cell preparations and analysed using flow cytometry. Prior to scrapie challenge, significantly more PrP(+) cells were detected in PBMCs from the susceptible sheep. Furthermore, following challenge, significantly more CD8(+) and gammadelta(+) T cells were detected in the PBMCs of the resistant sheep. However, at both 14 and 180 days p.i, CD21(+) cell expression was significantly higher in the lymph node preparations of the susceptible sheep. In contrast, more CD4(+) cells were detected in the lymph nodes of the resistant sheep at both time points. It was concluded that significant differences in immune cell subsets and PrP expression occur between ARQ/ARQ and ARR/ARR Suffolk sheep in the preclinical phase of infection.
Journal of General Virology 05/2007; 88(Pt 4):1384-91. · 3.36 Impact Factor
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FEMS Immunology & Medical Microbiology 01/2006; 8(1):1 - 12. · 2.44 Impact Factor
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Journal of Animal Ecology 06/2004; 73(4):811 - 813. · 4.94 Impact Factor
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ABSTRACT: The alcelaphine herpesvirus 1 (AlHV-1) causes malignant catarrhal fever in ruminants. Previous work had shown that serial passage of AlHV-1 in culture resulted in genome alterations that are associated with a loss in pathogenicity. Here we have analysed the re-arrangements that occur in more detail. None of the observed re-arrangements was entirely consistent. However, they did all involve translocation of a similar region of DNA from around the centre of the genome to areas either next to or in between terminal repeat elements at either end of the genome. There was also a concomitant loss of the wild-type locus. These re-arrangements appeared to be associated with the loss of virulence and the appearance of cell-free virus.
Research in Veterinary Science 11/2003; 75(2):163-8. · 1.65 Impact Factor
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ABSTRACT: The alcelaphine herpesvirus 1 (AlHV-1) causes malignant catarrhal fever in ruminants. Previous work had shown that serial passage of AlHV-1 in culture resulted in genome alterations that are associated with a loss in pathogenicity. Here we have analysed the re-arrangements that occur in more detail. None of the observed re-arrangements was entirely consistent. However, they did all involve translocation of a similar region of DNA from around the centre of the genome to areas either next to or in between terminal repeat elements at either end of the genome. There was also a concomitant loss of the wild-type locus. These re-arrangements appeared to be associated with the loss of virulence and the appearance of cell-free virus.
Research in Veterinary Science 03/2003; 75(2):163-168. · 1.65 Impact Factor
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Journal of Animal Ecology 02/2003; 72(1):177 - 185. · 4.94 Impact Factor
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ABSTRACT: An outbreak of malignant catarrhal fever (MCF) resulted in the deaths of 12 cattle in a herd of 77 animals during seven weeks in 1999; in addition, one cow developed a milder disease which was confirmed as MCF by PCR for ovine herpesvirus 2 DNA and an immunofluorescent antibody test for antibodies to the virus, but recovered. Further PCR and serological testing revealed the infection in three other animals, none of which developed clinical disease. Hypocuprosis and the possibility of a genetic predisposition were identified as factors which may have contributed to the outbreak.
The Veterinary record 10/2002; 151(11):321-4. · 1.25 Impact Factor
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Journal of Animal Ecology 03/2002; 70(6):1053 - 1061. · 4.94 Impact Factor
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ABSTRACT: In sheep infected with the parapoxvirus orf virus, primary infection orf skin lesions developed and resolved within 8 weeks. Reinfection lesions were smaller and resolved within 3 weeks. The host response in the skin was characterized by an accumulation of neutrophils, dendritic cells, CD4+ T cells, CD8+ T cells, B cells and T19+ gammadelta T cells. The magnitude of this accumulation paralleled orf virus replication in the skin. In situ hybridization was used to detect cells expressing interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) mRNAs in orf skin. Cells expressing IL-4 mRNA were not detected at any time after infection. Cells expressing IFN-gamma mRNA were detected after reinfection but not after primary infection. Cells expressing TNF-alpha mRNA included epidermal cells, vascular endothelium and uncharacterized cells that increased more rapidly in the skin after reinfection compared to primary infection. The results are consistent with a prominent role for IFN-gamma in the host immune response controlling the severity of the disease.
Veterinary Immunology and Immunopathology 01/2002; 83(3-4):161-76. · 2.08 Impact Factor
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ABSTRACT: Three parapoxviruses which cause orf or related diseases in humans and animals and the orthopoxvirus, vaccinia virus, were tested for their in vitro sensitivity to cidofovir. The 50% inhibitory concentration for the three parapoxviruses was between 0.21 and 0.27 microg/ml and for vaccinia was 1.32 microg/ml. The selectivity index varied from 198 to 264 for the parapoxviruses and was 42 for vaccinia virus. Virus yield assays confirmed the ability of cidofovir to reduce ortho- and parapoxvirus replication. The efficacy of cidofovir against parapoxviruses justifies its evaluation as a candidate drug for the treatment of parapoxvirus infections in humans and animals.
Antiviral Research 01/2001; 48(3):205-8. · 4.30 Impact Factor
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ABSTRACT: Louping-ill (LI) is a tick-borne viral disease of red grouse, Lagopus lagopus scoticus Lath. (Tetraonidae: Galliformes), and sheep, Ovis aries L. (Bovidae: Artiodactyla), that causes economic loss to upland farms and sporting estates. Unvaccinated sheep, grouse and mountain hares, Lepus timidus L. (Leporidae: Lagomorpha), are known to transmit LI virus, whereas red deer, Cenrus elaphus L. (Cervidae: Artiodactyla), and rabbits, Oryctolagus cuniculus L. (Leporidae: Lagomorpha), do not. However, the role of small mammals is unknown. Here, we determine the role of small mammals, in particular field voles, Microtus agrestis L. (Muridae: Rodentia), in the persistence of LI virus on upland farms and sporting estates in Scotland, using field sampling and non-viraemic transmission trials. Small mammals were not abundant on the upland sites studied, few ticks were found per animal and none of the caught animals tested seropositive to LI virus. Laboratory trials provided no evidence that small mammals (field voles, bank voles, Clethrionomys glareolus L. (Muridae: Rodentia), and wood mice, Apodemus sylvaticus L. (Muridae: Rodentia), can transmit LI virus between cofeeding ticks and, in the field, LI virus was prevalent only in areas with known LI virus competent hosts (grouse, mountain hares or unvaccinated sheep) and absent elsewhere. In contrast to the case of tick-borne encephalitis (TBE) virus in Europe, it is concluded that small mammals seem to be relatively unimportant in LI virus persistence.
Medical and Veterinary Entomology 10/2000; 14(3):277-82. · 1.91 Impact Factor
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ABSTRACT: In some areas of Scotland, the prevalence of louping-ill virus has not decreased despite the vaccination of replacement ewes for over 30 years. The role of unvaccinated lambs in viral persistence was examined through a combination of an empirical study of infection rates of lambs and mathematical modelling. Serological sampling revealed that most lambs were protected by colostral immunity at turnout in May/June but were fully susceptible by the end of September. Between 8 and 83% of lambs were infected over the first season, with seroconversion rates greater in late rather than early summer. The proportion of lambs that could have amplified the louping-ill virus was low, however, because high initial titres of colostral antibody on farms with a high force of infection gave protection for several months. A simple mathematical model suggested that the relationship between the force of infection and the percentage of lambs that became viraemic was not linear and that the maximum percentage of viraemic lambs occurred at moderately high infection rates. Examination of the conditions required for louping-ill persistence suggested that the virus could theoretically persist in a sheep flock with over 370 lambs, if the grazing season was longer than 130 days. In practice, however, lamb viraemia is not a general explanation for louping-ill virus persistence as these conditions are not met in most management systems and because the widespread use of acaracides in most tick-affected hill farming systems reduces the number of ticks feeding successfully.
Parasitology 03/2000; 120 ( Pt 2):97-104. · 2.96 Impact Factor
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ABSTRACT: The causal agent of sheep-associated malignant catarrhal fever (MCF), Ovine Herpesvirus-2 (OHV-2), can be propagated in IL-2-dependent lymphoblastoid cell lines derived from diseased cattle and deer providing a useful model for the investigation of the pathogenesis of MCF. In this study, five interleukin-2 (IL-2)-dependent cell lines were established from affected cattle to examine their growth regulation and cytokine transcription. All cell lines expressed CD2, CD5 and CD25. Three of the cell lines were CD4+ and one CD8+, whereas one cell was of mixed CD4 and CD8 phenotye. The growth of these cell lines was reduced when cultured with antibody against CD25, the IL-2 receptor alpha subunit. All cell lines showed a lack of response to Con A and their cell growth was inhibited by Cyclosporin A which is known to inhibit cytokine promoters. It was decided therefore, to examine the cell lines for the presence of mRNA of different cytokines. The results showed that the cell lines transcribed message for IFNgamma, TNFalpha, IL-4 and IL-10 whereas no mRNA for IL-2 or IL-1beta was detected. In conclusion, the OHV-2-immortalised cell lines resemble anergic T-cells which may be activated giving rise to the characteristic lesions of MCF.
Veterinary Immunology and Immunopathology 12/1998; 66(1):67-81. · 2.08 Impact Factor
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ABSTRACT: A comparison of DNA profiles of representative isolates of orf virus, obtained using four different restriction endonucleases (RE), showed that the enzyme EcoRI could be used to discriminate between wild-type virus isolates and vaccine strains. The enzyme was used to compare the RE profiles of orf virus isolates from 43 outbreaks of orf that occurred in vaccinated flocks between 1988 and 1993; 21 outbreaks yielded wild-type virus, 10 yielded vaccine viruses, three produced both vaccine and wild-type viruses and no clear result was obtained from nine of the outbreaks. From the 21 outbreaks yielding wild-type viruses, 28 orf virus isolates had clear RE profiles and 15 distinct RE profiles were recorded. Usually only one virus type was associated with each outbreak but from two farms, two different wild-type viruses were recovered. No predominant genotype was identified, with four RE profile types being recovered for more than one outbreak. From the more severe form of orf involving the buccal cavities of lambs only wild-type viruses were recovered, with at least four different genotypes being represented.
The Veterinary record 09/1998; 143(9):237-40. · 1.25 Impact Factor
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ABSTRACT: The nucleotide and deduced amino acid sequences of louping ill (LI) virus isolates, collected from representative regions of the British Isles and Norway, were determined for either the entire envelope gene (20 isolates) or for a portion of the envelope gene that spans a hypervariable region and includes an LI virus specific marker sequence (53 isolates). Phylogenetic analysis reveals the presence of three major geographical populations of LI virus in the British Isles, viz. Irish, Welsh and British LI viruses, which all cause encephalomyelitis in animals, predominantly sheep, and co-habit the same tick population. British LI virus occurs throughout Scotland, England, Ireland and Norway. Irish and Welsh LI viruses occur only in Ireland and Wales, respectively. Phylogenetic analysis also predicts that LI virus initially emerged in Ireland and that a descendant was introduced into Great Britain via Wales and was subsequently transported to the borders of Scotland, from where it was dispersed throughout Scotland, northern England and Norway. More recently, the British LI virus was reintroduced into Ireland and also into south-west England. Dates of lineage divergence, calculated from the synonymous substitution rate, indicate that LI virus emerged in the British Isles less than 800 years ago and most LI virus dispersal occurred during the last 300 years. By combining these data with historical records it appears that livestock movement can be implicated in the dispersal of LI virus.
Journal of General Virology 06/1998; 79 ( Pt 5):981-8. · 3.36 Impact Factor
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ABSTRACT: A panel of 27 mouse monoclonal antibodies (Mabs) was raised against orf virus. Sixteen of these Mabs reacted with a protein with a molecular mass of 65 kDa, 8 reacted with a protein with a molecular mass of 39 kDa and three remain uncharacterised. Reactivity of the Mabs with a library of recombinant vaccinia viruses expressing various regions of the NZ-2 orf virus genome identified the approximate positions of the genes encoding these 2 immunodominant orf virus proteins. The gene encoding the 39 kDa protein was identified and sequenced. The protein was detected in an envelope fraction of orf virus and was shown to be homologous to the envelope protein encoded by the H3L gene of vaccinia virus. The 65 kDa protein has not been fully chracterised, but the gene encoding it has been localised to a 10 kbp region of the orf virus genome. The Mabs were used to discriminate 4 parapoxviruses derived from sheep, 2 from cattle and 1 each from a seal and squirrel. Eighteen Mabs reacted with all 4 sheep viruses, 19 Mabs reacted with both cattle viruses, 6 recognised seal parapoxvirus and 2 recognised the squirrel parapoxvirus. Only one of the 27 Mabs reacted with all 8 parapoxviruses suggesting it recognises a conserved epitope within the genus.
Archives of Virology 02/1998; 143(12):2289-303. · 2.11 Impact Factor
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ABSTRACT: Following the demonstration that the tick-borne encephalitis (TBE) subgroup viruses are distributed as a cline across the Northern Hemisphere (Zanotto et al., 1995), we have analyzed the dispersal pattern of louping ill (LI) virus, the most westerly located member in the cline. A total number of 21 LI or LI-related virus E gene sequences have been used for a detailed molecular analysis of the evolution, phylogeny and geographical distribution of LI virus in the British Isles and Ireland. The results show that LI virus is genetically stable in general but minor differences enable its separation into four genetically distinct subtypes (genotypes) with clear geographical correlation, designated Type 1 in Scotland and England, Type 2 in Scotland, Type 3 in Wales and Type 4 in Ireland. These data demonstrate that geographically independent evolution of LI viruses has occurred. The molecular systematics and substitutional parameters analyses combined with the clinal distribution of the TBE virus complex allow the assignment of the origin for both Negishi (NEG) virus and a Norwegian isolate to the British Isles. Moreover, proposals for the classification of LI and LI-like viruses which cause encephalomyelitis in sheep, goat or cattle are presented.
Acta virologica 11/1997; 41(5):259-68. · 0.68 Impact Factor
