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J Virol, March 1998, p. 1853-1861, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Lymphocyte Apoptosis during Classical Swine Fever: Implication of Activation-Induced Cell Death

Artur Summerfield,* Sonja M. Knötig, and Kenneth C. McCullough

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

Received 14 October 1997/Accepted 14 November 1997

Infection of pigs with classical swine fever virus (CSFV), a member of the Flaviviridae family, causes a severe leukopenia, particularly notable with the lymphocytes. The goal of this study was to analyze mechanisms behind this CSFV-induced lymphopenia. To this end, the kinetics of leukocyte depletion, the appearance of apoptotic cells, and virus infection of leukocytes after infection of pigs with the virulent CSFV strain Brescia were analyzed. Depletion of B and T lymphocytes was noted as early as 1 day postinfection (p.i.). Circulating viable lymphocytes with reduced mitochondrial transmembrane potential---a particular early marker for apoptosis---were also detectable as early as 1 day p.i. When isolated peripheral blood mononuclear cells were cultured for 6 h, significantly more sub-G1 cells with reduced DNA content were detected among the lymphocytes from CSFV-infected animals, again as early as 1 to 3 days p.i. The first time virus was first found in the plasma, as well as infection of leukocytes, was 3 days p.i. However, throughout the observation time of 1 week, <3% of the circulating leukocytes and no lymphocytes contained virus or viral antigen. Further analysis of the T lymphocytes from infected animals demonstrated an increase in CD49d, major histocompatibility complex class II, and Fas expression. An increased susceptibility to apoptosis in vitro was also observed, particularly after addition of concanavalin A as well as apoptosis-inducing anti-Fas antibody to the cultures. Taken together, these results imply that activation-induced programmed cell death was the mechanism behind lymphopenia during classical swine fever.

* Corresponding author. Mailing address: Institute of Virology and Immunoprophylaxis, Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland. Phone: 41-31-8489377. Fax: 41-31-8489222. E-mail: artur.summerfield{at}ivi.admin.ch.




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Copyright © 1998 by the American Society for Microbiology. All rights reserved.