|
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
|
