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New approaches to African swine fever virus (ASFV) diagnosis, pathogenesis and protection

Contract nr: FAIR-CT97-3441
Project nr: 3441
Project type: SC
Starting date: 01/01/1998
Duration: 42 months
Total cost: 1,328,350 EUR
EC Contribution: 1,048,250 EUR
Scientific Officer: Isabel MINGUEZ-TUDELA
Research topic: Animal health
Acronym: ASFV diagnosis, pathogenesis and protection

Background:
African Swine Fever (ASF) remains endemic in Sardinia as well as in large parts of Africa where it is currently growing explosively, posing a constant threat to European and world-wide pig farming. To control new outbreaks of the disease, as well as for the surveillance of free areas, rapid and reliable diagnostic tests are crucial.

Objectives:
One of the objectives of this project is to develop more sensitive tests for ASFV antibody detection, based on the use of recombinant virus proteins. The correlation between new outbreaks and the possible source of the virus strain has been very difficult to establish. A new approach to the molecular epidemiology of ASFV will be the characterisation of virus isolates by DNA sequencing. Understanding the pathogenesis of the disease will be another objective.

In acute ASF, alterations triggered by cytokines released by cells of the mononuclear phagocyte lineage, which are potent mediators of the inflammatory response, might contribute to the clinical symptoms observed. A determination of the cytokine profile in infected animals will provide information on the role that these bioactive factors play in the pathogenesis of the severe form of the disease.

Description:
In this context, the function of certain viral genes that might modulate the apoptosis of infected cells will also be studied. The knowledge of the sequence of the ASFV genome will allow us to design new strategies for the development of preventive tools for ASF.

Two viral genes encoding proteins that may be involved in the virus evasion of the host's immune response have therefore been identified. An important objective will be to define the role of these genes in the infection. On the other hand, the molecular characterisation of the cellular and viral components involved in the attachment and entry of the virus into the host cell may identify new targets for virus neutralisation. A study of the cellular immune response against ASFV infection will also be carried out, defining the role of T-Iymphocyte subpopulations and the cytokines produced in ASFV-specific responses. Finally, the development of vectors carrying specific ASFV genes will be of great importance to accomplish the proposed objectives.

Current situation/results:
The successful expression of a considerable number of recombinant ASFV proteins provides the necessary antigens to undertake the development of more sensitive tests for ASFV detection. On the other hand, the collection of a large number of virus isolates and sera from infected pigs will allow serological tests and DNA sequencing for the molecular epidemiology studies. The expression and functional studies carried out with the ASFV bcl-2 and iap homologues will contribute to our understanding of the role of these genes in the pathogenesis of ASFV.

The finding that the ASFV bcl-2 and IkB perform their function by mechanisms similar to those of the cellular homologues provides important information to understand their role in virus pathogenesis and may be useful for protection studies. A considerable progress in the development of the methodology necessary to carry out the studies of the cytokine profile and the T lymphocyte subpopulations involved in ASFV-specific response has been attained. The generation of antibodies against the ASFV protein B438L containing a RGD sequence, as well as the development of a hemolysis assay, will be useful to investigate the proteins involved in the early steps of infection. Important advances have also been obtained in the development of tools for the manipulation of the genome of virulent isolates of ASFV and for the construction of swinepox recombinants to be used in pathogenesis and protection studies.


Coordinator
Maria L. SALAS
Centro de Biologia Molecular "Severo Ochoa"
Universidad Autonoma de Madrid
Cantoblanco
E- 28049 Madrid
Tel: +34 91 397 84 78
Fax: +34 91 397 47 99
E-mail: mlsalas@cbm.uam.es


Partners

  • Gordon ALLAN
    Queens University
    Malone Road 8
    UK-BT9 5BN Belfast
    Tel: +44 1232 52 56 79
    Fax: +44 1232 52 57 73
    E-mail: Gordon.Allan@dani.gov.uk

  • Jose Manuel SANCHEZ-VIZCAINO RODRIGUEZ
    Instituto Nacional de Investigacion y Tecnologia Agrario y Alimentaria
    Carretera De La Corura Km. 7,5
    E-28040 Madrid
    Tel: +34 91 620 23 00
    Fax: +34 91 620 22 47
    E-mail: vizcaino@inia.es

  • Carlos MARTINS
    Seccion de doencas Infecto-Contagiosas
    Faculdade de Medicina Veterinaria
    Polo Universitario Alto de Ajuda
    Rua Professor Cid dos Santos
    P-13300-477 Lisbon
    Tel: +351 21 365 28 45
    Fax: +351 21 365 28 21
    E-mail: cmartins@fmv.utl.pt

  • Cristiana PATTA
    Istituto Zooprofilattico Sperimentale della Sardegna
    Via Duca Degli Abruzzi 8
    I- 07100 Sassari
    Tel: +39 079 28 92 31
    Fax: +39 079 27 21 89
    E-mail: cpatta@sardegna.izs.it

  • Pierre CORNELIS
    Vlaams Interuniversitair Instituut voor Biotechnologie
    Rijvisschestraat 118 Bus 1
    B-9052 Zwijnaarde
    Tel: +32 23 59 02 22
    Fax: +32 23 59 03 90
    E-mail: pcornel@vub.ac.be

  • Armin SAALMUELLER
    Bundesforschungsanstalt fuer Viruskrankheiten der Tiere
    Paul-Ehrlich Str. 28
    D-72076 Tuebingen
    Tel: +49 70 71 96 72 56
    Fax: +49 70 71 96 73 03
    E-mail: armin.saalmueller@tue.bfav.de

 
 
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