Home African Swine Fever [Host pathogen interactions] Host Pathogen interaction in ASF infection
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Roadmap for the development of a candidate vaccine for ASF

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Host pathogen interactions

Host pathogen interactions

Research Question

  • To gain an improved understanding of how ASFV enters, replicates and survives in and is released from infected cells

Research Gaps and Challenges

  • Establish how the virus interacts with macrophages as to identifying the protective mechanisms and how the virus evades them
  • Collect information on viral genomics/host transcriptomics and the determinants responsible for variations in virulence and protective responses
  • Identify viral receptors and ligands (identification, how virus interacts)
  • Identify viral attachment proteins
  • Determine patterns of activation of immunologically relevant host genes particularly at early stages after infection
  • Identify ASFV genes and genetic determinants (group of genes like multigene families) involved in host range, virulence and pathogenicity
  • Development of attenuated ASFV that can be classified as BSL2 agent.

Solution Routes

  • Establish the basis of virulence/pathogenicity – including in high virulence strains – and investigate its relationship with inflammatory response or viral replication
  • Identify ASFV genes and genetic determinants (group of genes like multigene families)
    involved in virulence and pathogenicity – including using knock-out or different strains
  • Assess viral and macrophage gene expression in different in vivo environments (macrophages from naïve and immune hosts)
  • Compare responses to highly pathogenic/virulent and mild/attenuated strains of the virus
  • Perform comparative genome studies with other large dsDNA viruses, including the
    Poxviridae
  • Identify regulatory genes involved in pro-inflammatory cytokines and antibodies production
    and the assessment of their actual role in the process of virus infection\virulence in swine

Dependencies

  • Genome sequence of various ASFV isolates

State Of the Art

  • The primary cell types infected by ASFV are those belonging to the mononuclearphagocytic system, including fixed tissue macrophages and specific lineages ofreticular cells
  • Pathological findings in acute ASF include leukopenia B and T cell lymphopenia /
    thrombocytopenia lymphocyte and mononuclear cell apoptosis
  • ASFV exhibit temporal regulation of gene expression
  • ASFV virions contain enzymatic activities that contribute to early events in, and
    activities critical for, viral replication in the cell cytoplasm, including RNA
    polymerase, nucleoside triphosphate phosphohydrolase, topoisomerase, mRNA
    capping, and protein kinase activity
  • ASFV encodes proteins predicted to mediate virus–host interaction, virulence, and
    mechanisms that enhance the ability of the virus to successfully replicate within
    the host, including homologs of cellular inhibitor of apoptosis (IAP), Bcl-2, I Kappa
    B (IKB) myeloid differentiation primary response antigen MyD116, lectin-like, and
    CD2 proteins

Projects

What activities are planned or underway?

Africa's Long Depression: The Growth and Debt Crises of 1975-2000

Planned Completion date 01/03/2027

Participating Country(s):

United KingdomIconUnited Kingdom