Induction of apoptosis in bone marrow neutrophil-lineage cells by classical swine fever virus.
The pathogenesis of bone marrow atrophy during classical swine fever (CSF) was investigated in vitro by using CSF virus (CSFV) infection of bone marrow haematopoietic cells (BMHC). The monocytic lineage had the highest susceptibility to CSFV infection, whereas the more mature SWC8(+) granulocytic cells were not directly susceptible to infection. However, myelomonocytic precursors were targets for CSFV infection and continued to differentiate into SWC8(+) granulocytic cells, which remained infected. This explains the occurrence of infected peripheral blood granulocytes during CSF. The infection of BMHC resulted in increased apoptosis and necrosis, mainly within the granulocytic lineage. Caspases 3 and 9 were particularly activated, relating to the mitochondrial pathway of apoptosis. Interestingly, the majority of infected cells were non-apoptotic, the apoptotic cells being primarily non-infected. This indicated an indirect mechanism for induction of apoptosis, but no role could be identified for bone marrow stroma cells such as macrophages or fibroblastoid cells. Furthermore, soluble factors including cytokines and reactive oxygen species were not primarily responsible. In contrast, contact between infected and non-infected BMHC was critical for increasing apoptosis in the latter. Taken together, these results in vitro relate to and help to explain further the apoptosis of BMHC that occurs in vivo during CSF. This experimental system will also be particularly useful for the study of CSFV gene products involved in leukocyte apoptosis.
Summerfield
Artur
A
Institute of Virology and Immunoprophylaxis, Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland1.
Zingle
Katy
K
Institute of Virology and Immunoprophylaxis, Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland1.
Inumaru
Shigeki
S
Laboratory of Bioengineering, National Institute of Animal Health, Ibaraki 305, Japan2.
McCullough
Kenneth C
KC
Institute of Virology and Immunoprophylaxis, Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland1.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001685:Biological Factors / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000821:virology*; D020169:Caspases / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006692:Classical Swine Fever Virus / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000821:virology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000821:virology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D013552:Swine / Q000821:virology
D001685:Biological Factors; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020169:Caspases