The Pirbright Institute publication directory contains details of selected publications written by our researchers.

There were a total of 1662 results for your search.
McCormick J, Flower D R, Strobel S, Wallace D L, Beverley P C L, Tchilian E Z (2003)

Novel perforin mutation in a patient with hemophagocytic lymphohistiocytosis and CD45 abnormal splicing

American Journal of Medical Genetics Part A 117A (3), 255-260


Hemophagocytic lymphohistiocytosis (HLH) composes a group of rare heterogenous disorders characterized by uncontrolled accumulation and infiltration of activated T lymphocytes and macrophages. Cytotoxic T and natural killer cell activity is significantly reduced or absent in these patients. Mutations in the important mediator of lymphocyte cytotoxicity perforin were identified in a number of HLH individuals. Here we report a novel missense mutation thr435met in the conserved Ca2+ binding domain of perforin in a patient with HLH. Prediction of the 3-dimensional structure of the thr435met perforin mutant using comparative molecular modeling indicates that the protein's ability to bind Ca2+, and therefore its cytolytic function, would be strongly compromised. In addition, this patient exhibited abnormal CD45 splicing caused by a C77G mutation in the gene encoding CD45 (PTPRC). Our findings suggest a combined role for perforin mutation and abnormal CD45 splicing as significant contributory factors in the pathogenesis of HLH.
Gomez-Villamandos J C, Carrasco L, Bautista M J, Sierra M A, Quezada M, Hervas J, De Lara F C M, Ruiz-Villamor E, Salguero F J, Sanchez-Cordon P J, Romanini S, Nunez A, Mekonen T, Mendez A, Jover A (2003)

African swine fever and classical swine fever: a review of the pathogenesis

Deutsche Tierarztliche Wochenschrift 110 (4), 165-169


This paper describes major pathogenetic mechanisms of African and Classical Swine Fever virus infections. The interactions between both viruses and the monocyte-macrophage-system result in the release of mediator molecules, which are important for the further progression of the diseases. The causes of the thrombocytopenia and the mechanisms of the haemorrhages, which are characteristic in both infections, are described. Apoptotic cell death is regarded as the predominant cause of lymphopenia in both virus infections.

Barrett T, Parida S, Mohaptra M, Walsh P, Das S, Baron M D (2003)

Development of new generation rinderpest vaccines

Developments in Biologicals 114, 89-97


Veterinary science has benefited much from the advances in biotechnology during the past 20 years. New and improved diagnostic techniques for infectious diseases have been developed and new and highly effective vaccines to prevent such diseases have been introduced and more have been, or are about to be, field-tested. The latest development in negative strand virology, reverse genetics, the ability to rescue live virus from a DNA copy of the RNA genome, is being used to address questions concerning virus pathogenicity at the molecular level and to produce "marker" vaccines, i.e. vaccines that allow serological identification of all vaccinated animals. Such a vaccine would greatly benefit the continuing campaign for the global eradication of rinderpest since it would then be possible, by serological means, to detect wild type virus circulating in local areas or regions where it is still necessary to vaccinate and where the vaccination levels are below those required to eliminate the virus. Here we describe different approaches we have taken to produce such a vaccine using reverse genetics to add a marker to the existing and widely used Plowright rinderpest vaccine

Beard P M, Taus N S, Baines J D (2002)

DNA cleavage and packaging proteins encoded by genes U(L)28, U(L)15, and U(L)33 of herpes simplex virus type 1 form a complex in infected cells

Journal of Virology 76 (10), 4785-4791


Previous studies have indicated that the U(L)6, U(L)15, U(L)17, U(L)28, U(L)32, and U(L)33 genes are required for the cleavage and packaging of herpes simplex viral DNA. To identify proteins that interact with the U(L)28-encoded DNA binding protein of herpes simplex virus type 1 (HSV-1), a previously undescribed rabbit polyclonal antibody directed against the U(L)28 protein fused to glutathione S-transferase was used to immunopurify U(L)28 and the proteins with which it associated. It was found that the antibody specifically coimmunoprecipitated proteins encoded by the genes U(L)28, U(L)15, and U(L)33 from lysates of both HEp-2 cells infected with HSV-1(F) and insect cells infected with recombinant baculoviruses expressing these three proteins. In reciprocal reactions, antibodies directed against the U(L)15- or U(L)33-encoded proteins also coimmunoprecipitated the U(L)28 protein. The coimmunoprecipitation of the three proteins from HSV-infected cells confirms earlier reports of an association between the U(L)28 and U(L)15 proteins and represents the first evidence of the involvement of the U(L)33 protein in this complex.

Bell-Sakyi L, Paxton E, Wright P, Sumption K (2002)

Immunogenicity of Ehrlichia ruminantium grown in tick cell lines

Experimental and Applied Acarology 28 (1), 177-185


Ehrlichia (previously Cowdria) ruminantium, the pathogen which causes heartwater in domestic and wild ruminants, can now be propagated in cell lines from one vector (Amblyomma variegatum) and five non-vector (Ixodes scapularis, I. ricinus, Boophilus decoloratus, B. microplus and Rhipicephalus appendiculatus) tick species. E. ruminantium isolates from West and South Africa and the Caribbean vary in their cell line preference, growth patterns and immunogenic capability. In laboratory trials, certain combinations of tick cell line and E. ruminantium isolate were highly immunogenic in sheep. These trial vaccines were grown under specific in vitro conditions and administered as a single intravenous dose of freshly harvested whole, live culture. Following immunisation and subsequent exposure to virulent E. ruminantium, protected sheep showed no clinical response and a range of serological responses.
Weber F, Bridgen A, Fazakerley J K, Streitenfeld H, Kessler N, Randall R E, Elliott R M (2002)

Bunyamwera Bunyavirus nonstructural protein NSs counteracts the induction of alpha/beta interferon

Journal of Virology 76 (16), 7949-7955


Production of alpha/beta interferons (IFN-?/?) in response to viral infection is one of the main defense mechanisms of the innate immune system. Many viruses therefore encode factors that subvert the IFN system to enhance their virulence. Bunyamwera virus (BUN) is the prototype of the Bunyaviridae family. By using reverse genetics, we previously produced a recombinant virus lacking the nonstructural protein NSs (BUNdelNSs) and showed that NSs is a nonessential gene product that contributes to viral pathogenesis. Here we demonstrate that BUNdelNSs is a strong inducer of IFN-?/?, whereas in cells infected with the wild-type counterpart expressing NSs (wild-type BUN), neither IFN nor IFN mRNA could be detected. IFN induction by BUNdelNSs correlated with activation of NF-?B and was dependent on virally produced double-stranded RNA and on the IFN transcription factor IRF-3. Furthermore, both in cultured cells and in mice lacking a functional IFN-?/? system, BUNdelNSs replicated to wild-type BUN levels, whereas in IFN-competent systems, wild-type BUN grew more efficiently. These results suggest that BUN NSs is an IFN induction antagonist that blocks the transcriptional activation of IFN-?/? in order to increase the virulence of Bunyamwera virus.
Salguero F J, Sanchez-Cordon P J, Nunez A, Gomez-Villamandos J C (2002)

Histopathological and ultrastructural changes associated with herpesvirus infection in waterfowl

Avian Pathology 31 (2), 133-140


Duck virus enteritis is an acute contagious viral disease affecting birds of the order Anseriformes (ducks, geese and swans). The disease agent is a member of the Herpesviridae family (Anatidae herpes virus 1). A group of Anseriformes waterfowl from a Nature Reserve and Centre for the Recovery of Endangered Species in Spain suffered an outbreak of the disease, affecting adults, young and newborns. Other non-Anseriformes waterfowl such as coots, from the family Rallidae, order Gruiformes, were also affected. Histopathological and ultrastructural findings confirmed the viral infection. The present study provides evidence that birds different from the order Anseriformes can be affected, suggesting that the virus has the ability to infest other non-Anseriformes waterfows.
Iqbal M, McCauley J W (2002)

Identification of the glycosaminoglycan-binding C2 - on the glycoprotein Erns of bovine viral diarrhoea virus by site-directed mutagenesis

Journal of General Virology 83 (9), 2153-2159


Bovine viral diarrhoea virus (BVDV) envelope glycoprotein Erns interacts with highly sulphated heparin-like glycosaminoglycans (GAGs) located on the cell surface as an early step in virus infection of cells. Site-directed mutagenesis of recombinant Erns was undertaken and analysis of mutants by heparin-affinity chromatography and cell surface binding showed that a cluster of basic amino acids (480KKLENKSK487) near the C terminus of Erns was essential for binding. Mutants with amino acid substitutions of lysine residues 481 and 485 in Erns reduced the binding of Erns to immobilized heparin and cellular GAGs but retained ribonuclease activity. In contrast to normal Erns, Erns that was unable to bind to cells also failed to inhibit BVDV infection of cells when the cells were pre-incubated with Erns. It is proposed that the cluster of basic residues (480KKLENKSK487) localized at the C-terminal end of Erns constitutes a GAG-binding site.
Carrasco L, Nunez A, Salguero F J, San Segundo F D, Sanchez-Cordon P, Gomez-Villamandos J C, Sierra M A (2002)

African swine fever: Expression of interleukin-1 alpha and tumour necrosis factor-alpha by pulmonary intravascular macrophages

Journal of Comparative Pathology 126 (2-3), 194-201


To determine. in the acute form of African swine fever (ASF), the relationship between the appearance of pulmonary oedema and viral replication and expression of cytokines by pulmonary intravascular macrophages (PIMs), 14 pigs were inoculated intramuscularly with ASF virus (strain Espana' 70) and killed in pairs on days 1-7 post-inoculation. Samples of lung were examined immunohistochemically and ultrastructurally. The immunohistochemical study was carried out with antibodies against interleukin-1 alpha IL-1alpha, tumour necrosis factor-alpha TNF-alpha), viral antigen of ASF (Vp73) and a myeloid marker (SWC3). Viral replication was observed mainly in PIMs, which at the same time showed intense activation. accompanied by the expression of IL-1alpha and TNF-alpha. The occurrence of interstitial oedema, neutrophil sequestration and fibrin microthrombi in septal capillaries coincided with high degrees of cytokine expression by infected PIMs. Alveolar macrophages did not show a significant change in cytokine expression as a result of ASF infection, and viral replication was detected in only a low percentage of these cells. (C) 2002 Elsevier Science Ltd.
Sanchez-Cordon P J, Hervas J, de Lara F C, Jahn J, Salguero F J, Gomez-Villamandos J C (2002)

Reovirus infection in psittacine birds (Psittacus erithacus): Morphologic and immunohistochemical study

Avian Diseases 46 (2), 485-492


In this paper we report on an outbreak of reovirus, herpesvirus (Pacheco disease), and/or mycosis infection (Aspergillus spp. and Zygomyces spp.) affecting a batch of young African grey parrots (Psittacus erithacus), with 80% morbidity and 30% mortality. Study material was taken from five birds (four dead and one euthanatized) with a range of clinical symptoms (depression, diarrhea, respiratory symptoms). Diagnosis was confirmed by immunohistochemical detection of avian reovirus, electron microscopy, and virus isolation. Viral antigen of reovirus was detected mainly in large mononuclear cells in the bursa of Fabricius and the spleen, pancreas epithelia-l cells, and circulating cells; lymphoid organs displayed the largest number of immunopositive cells and severe lymphocyte depletion. Bacteriologic study was negative. Reovirus infection was common in all birds studied, whereas Pacheco disease and mycosis were found in only some, suggesting that reovirus could be the initial cause triggering the outbreak and facilitating infection by other agents and their swift spread through the batch.


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