African swine fever virus multigene family 360 and 530 genes are novel macrophage host range determinants

L Zsak1, Z Lu, T G Burrage

  • 1Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944-0848, USA. lzsak@piadc.ars.usda.gov

Journal of Virology
|March 10, 2001
PubMed

Insights

African swine fever virus (ASFV) adapted to grow in monkey cells causes early macrophage death. Specific ASFV genes, MGF 360 and MGF 530, are crucial for viral replication in macrophages.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Pathogenic African swine fever virus (ASFV) primarily infects swine macrophages.
  • ASFV can be adapted to grow in non-macrophage cell lines, like monkey cells.
  • The host range and replication efficiency of ASFV are key areas of study.

Purpose of the Study:

  • To identify the genetic factors responsible for ASFV's macrophage host range.
  • To understand the mechanism by which adapted ASFV strains cause early cell death in macrophages.
  • To pinpoint specific ASFV genes essential for replication in macrophage cell cultures.

Main Methods:

  • Characterization of cell culture-adapted ASFV strains (MS16, BA71V) in macrophage cultures.
  • Cell viability assays and ultrastructural analysis to assess infection effects.
  • Marker rescue experiments using genomic cosmid clones from pathogenic ASFV E70.
  • Fine-mapping of essential viral regions and sequence analysis.
  • Deletion mutagenesis of specific ASFV genes in a pathogenic isolate (Pr4).

Main Results:

  • Cell culture-adapted ASFV strains (MS16, BA71V) induced rapid macrophage cell death before viral replication.
  • A 38-kbp genomic region from pathogenic ASFV E70 restored MS16 and BA71V growth in macrophages.
  • An 11-kbp subclone within this region was sufficient for rescuing BA71V growth.
  • MS16 and BA71V exhibited deletions in the MGF 360 and MGF 530 gene families.
  • Deletion of the MGF 360/530 region from pathogenic ASFV Pr4 significantly reduced its growth in macrophages.

Conclusions:

  • ASFV multigene families 360 (MGF 360) and 530 (MGF 530) are critical for macrophage host range.
  • These ASFV genes play an essential role in promoting the survival of infected macrophages.
  • Understanding these genes is vital for controlling ASFV pathogenesis and host adaptation.

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