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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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