Pathogenesis of Granulocytopenia and Bone Marrow Atrophy during Classical Swine Fever Involves Apoptosis and Necrosis of Uninfected Cells

Authors: Summerfield A.; Knoetig S.M.; Tschudin R.; McCullough K.C.

Source: Virology, Volume 272, Number 1, June 2000 , pp. 50-60(11)

Publisher: Academic Press

Abstract:

Granulocytopenia, a hematological hallmark of classical swine fever, is partially responsible for the suppression of innate immune defenses during classical swine fever. The present report demonstrates that this depletion was apparent as early as 3 days postinfection (p.i.). Both mature peripheral and bone marrow neutrophils were affected, whereas immature neutrophils increased absolutely in the periphery and coincidentally immature myeloid progenitors in the bone marrow. These data suggest that a pathogenic relationship exists between these compartments. The central event was not the arrest of hematopoietic cell proliferation or of the mobilization process, but instead apoptosis and possibly also necrosis were shown to play a role. This increase in apoptotic and dead cells was detected as early as 1–3 days p.i. In contrast, viral RNA in bone marrow hematopoietic cells (BMHC) was first detected 5 days p.i., and significant amounts of infected BMHC were detected only 7 days p.i., with the major target being the myeloid compartment. The increased caspase-3 activity observed supported a role for apoptotic cell death. Furthermore, the elevated caspase-9 activity indicated the involvement of the mitochondrial apoptotic pathway. Taken together, the results demonstrate that granulocytopenia and bone marrow atrophy are mediated by hematopoietic cell death and that indirect virus–host-mediated mechanisms are likely to be responsible. Copyright 2000 Academic Press.

Keywords: granulocytopenia; bone marrow atrophy; apoptosis; necrosis; caspases; hematopoiesis; classical swine fever

Language: English

Document Type: Research article

Affiliations: Institute of Virology and Immunoprophylaxis, Mittelhäusern, CH-3147, Switzerland

Publication date: 2000-06-01

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• In this Subject: Microbiology ,  Internal Medicine
• By this author: Summerfield A. ;  Knoetig S.M. ;  Tschudin R. ;  McCullough K.C.

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