TB policy and the badger culling trials.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
W I Morrison
Publications and source records attributed to W I Morrison.
TB policy and the badger culling trials.
Explore the source record for details and available documents.
Animals↗
Analysis of T-cell receptor BV gene sequences in cattle reveals extensive duplication within the BV9 and BV20 subgroups.
We investigated the repertoire of functional T-cell receptor beta-chain variable genes (TRBV genes) in cattle by analysing the nucleotide sequences and predicted amino acid sequences of a set of cDNA clones isolated from lymph node T cells. Thirty-nine distinct TRBV sequences were identified, bringing the total number of recognised bovine TRBV gene segments to more than 40. Sixteen TRBV subgroups were defined based on their sequence homology to each other and to human TRBV genes. All of the main phylogenetic lineages of BV gene subgroups described in humans and mice were represented. Eight of the subgroups were found to contain more than one member. The most striking feature of the results was the large number of sequences (more than half of the sequenced clones) in the BV9 and BV20 subgroups, which were found to contain 12 and 8 distinct sequences, respectively. In contrast, the corresponding human TRBV subfamilies contain a single member. The results indicate that, as in humans, there has been extensive gene duplication within the TRBV locus during evolution. However, duplication of different BV subgroups in cattle has resulted in a TRBV gene repertoire distinct from that found in other species.
Amino Acid Sequence↗
Herd-level risk factors associated with tuberculosis breakdowns among cattle herds in England before the 2001 foot-and-mouth disease epidemic.
A case-control study of the factors associated with the risk of a bovine tuberculosis (TB) breakdown in cattle herds was undertaken within the randomized badger culling trial (RBCT). TB breakdowns occurring prior to the 2001 foot-and-mouth disease epidemic in three RBCT triplets were eligible to be cases; controls were selected from the same RBCT area. Data from 151 case farms and 117 control farms were analysed using logistic regression. The strongest factors associated with an increased TB risk were movement of cattle onto the farm from markets or farm sales, operating a farm over multiple premises and the use of either covered yard or 'other' housing types. Spreading artificial fertilizers or farmyard manure on grazing land were both associated with decreased risk. These first case-control results from the RBCT will be followed by similar analyses as more data become available.
Animals↗
Potential use of vaccination in cattle or badgers to control bovine tuberculosis.
The application of regular herd testing to identify and remove infected animals has proved to be a highly successful method of controlling bovine tuberculosis (TB) in many parts of the world. However, in some countries, notably the United Kingdom, Ireland and New Zealand, the disease has continued to pose a significant problem, despite intensive herd testing. Persistence of disease in these countries is associated with the presence of wildlife reservoirs of infection. Attempts to control bovine TB by culling of wildlife have been, at best, only partially successful and have proved difficult to sustain. This has led to considering of vaccination either of wildlife or cattle as a potential control measure. However, there are a number of obstacles that need to be overcome before vaccination can be considered a practical option. Vaccine efficacy, methods used for vaccine delivery in wildlife, potential interference of vaccination with diagnostic tests for cattle and appropriate design of field trials are among the issues that need to be addressed.
Animals↗
Analysis of the repertoire of cattle CD4(+) T cells reactive with bovine viral diarrhoea virus.
Cell-mediated immunity and CD4(+) cells in particular are important for the resolution of acute infection with non-cytopathic bovine viral diarrhoea virus (BVDV). CD4(+) T cells were shown to recognise virus-infected and non-infectious-protein-pulsed APCs, whereas CD8(+) T cells recognised only virus-infected APCs. T cell recognition was strain cross-reactive and MHC-restricted. Using native and recombinant antigens, we identified the structural glycoprotein E2 and the non-structural protein NS3 as dominant CD4(+) T cell determinants. The repertoire of CD4(+) T cell responses to E2 and NS3 was examined using inbred, homozygous cattle and overlapping synthetic peptides. The repertoire was biased toward conserved regions of NS3 and excluded the hypervariable regions of E2. The number of peptides that were recognised varied between animals but patterns could be distinguished in those animals that shared the same DRB3(*) allele. Of particular interest were: (i) a determinant that was recognised in the context of both DRB3(*) alleles (i.e. DRB3(*)2002 and DRB3(*)0701), (ii) two determinants that were juxtaposed to B cell sites, and (iii) a determinant that had structural analogy with a NS3 epitope previously described for the closely related hepatitis C virus. The minimum stimulatory sequence of the latter, NS3(397-414), was located to residues NS3(400-410).
Amino Acid Sequence↗
Alpha/beta and gamma interferons are induced by infection with noncytopathic bovine viral diarrhea virus in vivo.
In contrast to the results of previous in vitro studies, experimental infection of calves with noncytopathic bovine viral diarrhea virus (ncpBVDV) was found to induce strong alpha/beta and gamma interferon responses in gnotobiotic animals. These responses were associated with depressed levels of transforming growth factor beta (TGF-beta) in serum. The results of this study indicate that the immunosuppression caused by ncpBVDV is not associated with low interferon responses or elevated levels of TGF-beta.
Acute Disease↗
Establishment of persistent infection with non-cytopathic bovine viral diarrhoea virus in cattle is associated with a failure to induce type I interferon.
The establishment of persistent infections with non-cytopathic bovine virus diarrhoea virus (ncpBVDV) is crucial for the maintenance of BVDV in cattle populations. Also, super-infection of persistently infected individuals with antigenically homologous cytopathic BVDV (cpBVDV) results in fatal mucosal disease. Persistent infection with ncpBVDV is established by infection of the foetus during the first trimester of pregnancy. It has been shown previously that foetal infection with cpBVDV does not result in persistent infection. Infection of cells in vitro has demonstrated that cpBVDV induces type I interferon (IFN), whereas ncpBVDV fails to induce IFN. In this study we demonstrate that foetal challenge with cpBVDV results in IFN production, whereas ncpBVDV does not. These findings strongly suggest that the ability of ncpBVDV to inhibit the induction of type I IFN has evolved to enable the virus to establish persistent infection in the early foetus.
Amniotic Fluid↗
Single amino acid differences are sufficient for CD4(+) T-cell recognition of a heterologous virus by cattle persistently infected with bovine viral diarrhea virus.
Cattle that are persistently infected (PI) with one strain of bovine viral diarrhea virus (BVDV) can resolve infection with a second, antigenically heterologous strain but not the homologous strain. Since CD4(+) T cells are thought to be critical for the resolution of acute BVDV infection (Howard et al., 1992, Vet. Immunol. Immunopathol. 32, 303-314), we have examined the recognition of a heterologous virus (NADL) by CD4(+) T cells from Pe515-PI animals. The immune response of non-PI control cattle challenged with NADL or Pe515ncp was strain cross-reactive, whereas Pe515-PI animals responded to NADL only. The immune repertoire of both groups included NS3, which differs by approximately 1% (9/683) amino acids between these two viruses. Lymphoproliferative responses to proteins and synthetic peptides corresponding to three nonconservative differences in NS3 demonstrated that CD4(+) T cells from non-PI control animals responded well to proteins but poorly to the peptides from both viruses. In contrast, PI animals were responsive to heterologous proteins and peptides but nonresponsive to the homologous equivalents. A single amino acid difference between the two sequences was sufficient to allow responsiveness.
Amino Acid Sequence↗
Pathogenesis and diagnosis of infections with Mycobacterium bovis in cattle. Independent Scientific Group on Cattle TB.
In last week's Veterinary Record, members of the Independent Scientific Group on Cattle TB discussed the approach they are adopting in attempting to develop sustainable strategies for controlling bovine tuberculosis in cattle (VR, February 19, pp 207-210). In this second, complementary article, they consider the extent to which efforts to control the disease may be constrained by limitations in current testing procedures.
Animals↗
Follicular dendritic cells in scrapie pathogenesis.
Scrapie pathogenesis was studied in chimaeric mice that carried the prion protein (PrP) gene only in particular cells of the immune system. These mice were produced by grafting bone marrow from PrP expressing donors into PrP deficient recipients and vice versa. As follicular dendritic cells are not replaced significantly from the bone marrow in adult mice, this procedure resulted in a mismatch in PrP genotype between these cells and bone marrow derived cells such as lymphocytes. Using these models we obtained strong evidence that follicular dendritic cells produced high levels of the normal form of PrP in uninfected mice. Furthermore, the replication of a mouse-passaged scrapie strain in the spleen depended only on the presence of PrP expressing follicular dendritic cells. PrP expression by lymphocytes or other bone marrow derived cells had no influence on replication in spleen or on neuroinvasion in these models. These results indicate that the follicular dendritic cell is a potential target for prophylactic or therapeutic intervention in transmissible spongiform encephalopathies.
Animals↗
CD4(+) T-cell responses to bovine viral diarrhoea virus in cattle.
Friesian calves were infected with one of three isolates of bovine viral diarrhoea virus (BVDV) and used to establish parameters for an in vitro model of BVDV-reactive T-cell responses in cattle. The study assessed virus clearance, seroconversion, maturation of lymphoproliferative responses (both during and following disease resolution) and the antigen-specificity of CD4(+) T cells from recovered animals. Seroconversion and virus-specific lymphoproliferation were not detected until viraemia had resolved. Interestingly, lymphoproliferation was detected earlier in the animals infected with cytopathic viruses than in those infected with noncytopathic virus despite broadly similar rates of virus clearance and seroconversion for both biotypes. CD4(+) and CD8(+) T cells were induced to proliferate by virus-infected stimulator cells whereas only CD4(+) T cells responded to non-infectious antigens. Lymphoproliferation was strain cross-reactive and MHC-restricted. Induction of T-cell proliferation by recombinant proteins identified the major envelope proteins E(rns) and E2 and the nonstructural (NS) 2-3 protein as T-cell determinants. In addition, the capsid (C) and/or the amino-terminal proteinase, N(pro) were identified as T-cell determinants from the responses of short-term T-cell lines. Thus, in this model, the CD4(+) T-cell repertoire induce by acute BVDV infection includes at least the major envelope proteins, NS2-3, and capsid and/or N(pro).
Animals↗
Germinal centre localization of bovine viral diarrhoea virus in persistently infected animals.
Immunohistochemical analysis of peripheral lymph nodes from gnotobiotic calves persistently infected with bovine viral diarrhoea virus (BVDV) revealed extensive deposition of E(rns) and localization of the viral genome in the light zone of germinal centres. Viral antigen co-localized with immunoglobulin in the germinal centres and was shown to be extracellular. Despite the presence of viral antigen in germinal centres, circulating anti-BVDV antibody was not detected. These findings provide evidence that calves persistently infected with BVDV, in the absence of adventitious infection, can generate a B cell response to the persisting virus. The nature of the tolerance in calves persistently infected with BVDV is discussed in light of these findings.
Animals↗
Variation in the number of expressed MHC genes in different cattle class I haplotypes.
Analysis of cattle major histocompatibility complex (MHC) (BoLA) class I gene expression using serological and biochemical methods has demonstrated a high level of polymorphism. However, analysis of class I cDNA sequences has failed to produce conclusive evidence concerning the number and nature of expressed genes. Such information is essential for detailed studies of cattle immune responses, and to increase our understanding of the mechanisms of MHC evolution. In this study a selective breeding programme has been used to generate a number of MHC homozygous cattle expressing common serologically defined class I specificities. Detailed analysis of five class I haplotypes was carried out, with transcribed class I genes identified and characterized by cDNA cloning, sequence analysis, and transfection/expression studies. Surface expression of the gene products (on lymphocytes) was confirmed using monoclonal antibodies of defined BoLA specificity. Phylogenetic analysis of available transcribed cattle MHC class I sequences revealed complex evolutionary relationships including possible evidence for recombination. The study of individual haplotypes suggests that certain groupings of related sequences may correlate with loci, but overall it was not possible to define the origin of individual alleles using this approach. The most striking finding of this study is that none of the cattle class I genes is consistently expressed, and that in contrast to human, haplotypes differ from one another in both the number and composition of expressed classical class I genes.
Amino Acid Sequence↗
Contribution of advances in immunology to vaccine development.
During the last 10 years, investigation of the bovine immune system has generated knowledge and reagents that can now be applied to study the mechanisms of immunity to disease and the identity of antigens recognized by protective immune responses. Such studies can indicate which antigens are likely to be effective in subunit vaccines and also highlight the type of antigen delivery system that will be required for a vaccine to induce a protective immune response. In the case of bovine RSV, studies of immune responses in the target host have demonstrated that both antibody and CTL responses play an important role in immunity. Both the F and G glycoproteins have been identified as targets of protective antibodies, and systems have been established that will allow the identification of the viral antigens recognized by CTL. Further studies of CD4+ T-cell responses to the virus are required to determine whether or not components of the response have the potential to enhance disease and, therefore, need to be avoided in vaccination strategies.
Allergy and Immunology↗
Protective immune mechanisms against Theileria parva: evolution of vaccine development strategies.
Theileria parva is an intracellular sporozoan parasite that infects and transforms bovine lymphocytes, causing a severe lymphoproliferative disease known as East Coast fever in eastern, central and southern Africa. In this article, Declan McKeever and colleagues summarize the current understanding of immune mechanisms provoked by the parasite with regard to their role in both pathogenesis and protection. In particular, the influence of genomic polymorphism in parasite and host on the development of immunity is discussed, along with the evolution of current vaccine development strategies as a result of immunological research on the disease.
Animals↗
Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells.
The immune system is central in the pathogenesis of scrapie and other transmissible spongiform encephalopathies (TSEs) or 'prion' diseases. After infecting by peripheral (intraperitoneal or oral) routes, most TSE agents replicate in spleen and lymph nodes before neuroinvasion. Characterization of the cells supporting replication in these tissues is essential to understanding early pathogenesis and may indicate potential targets for therapy, for example, in 'new variant' Creutzfeldt-Jakob disease. The host 'prion' protein (PrP) is required for TSE agent replication and accumulates in modified forms in infected tissues. Abnormal PrP is detected readily on follicular dendritic cells (FDCs) in lymphoid tissues of patients with 'new variant' Creutzfeldt-Jakob disease, sheep with natural scrapie and mice experimentally infected with scrapie. The normal protein is present on FDCs in uninfected mice and, at lower levels, on lymphocytes. Studies using severe combined immunodeficiency (SCID) mice, with and without bone marrow (BM) grafts, have indicated involvement of FDCs and/or lymphocytes in scrapie pathogenesis. To clarify the separate roles of FDCs and lymphocytes, we produced chimeric mice with a mismatch in PrP status between FDCs and other cells of the immune system, by grafting bone marrow from PrP-deficient knockout mice into PrP-expressing mice and vice versa. Using these chimeric models, we obtained strong evidence that FDCs themselves produce PrP and that replication of a mouse-passaged scrapie strain in spleen depends on PrP-expressing FDCs rather than on lymphocytes or other bone marrow-derived cells.
Animals↗
Identification of seven new TCRBV subfamilies in cattle (Bos taurus).
In cattle, the repertoire of TCRBV genes that encode the variable region of T-cell receptor beta-chains has not been fully characterized. In this study, cattle TCRBV genes were amplified from mRNA by anchored polymerase chain reaction and sequenced. Eleven new TCRBV gene sequences were found, and classified into seven subfamilies distinct from those previously identified.
Amino Acid Sequence↗