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J Virol, April 1998, p. 2881-2889, Vol. 72, No. 4
Plum Island Animal Disease Center,
Agricultural Research Service, U.S. Department of
Agriculture, Greenport, New York 11944-0848
Received 17 October 1997/Accepted 31 December 1997
An African swine fever virus (ASFV) gene with similarity to the
T-lymphocyte surface antigen CD2 has been found in the pathogenic African isolate Malawi Lil-20/1 (open reading frame [ORF] 8-DR) and a
cell culture-adapted European virus, BA71V (ORF EP402R) and has been
shown to be responsible for the hemadsorption phenomenon observed for
ASFV-infected cells. The structural and functional similarities of the
ASFV gene product to CD2, a cellular protein involved in cell-cell
adhesion and T-cell-mediated immune responses, suggested a possible
role for this gene in tissue tropism and/or immune evasion in the swine
host. In this study, we constructed an ASFV 8-DR gene
deletion mutant (
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Deletion of a CD2-Like Gene, 8-DR, from
African Swine Fever Virus Affects Viral Infection in Domestic
Swine
8-DR) and its revertant (8-DR.R) from the Malawi
Lil-20/1 isolate to examine gene function in vivo. In vitro,
8-DR,
8-DR.R, and the parental virus exhibited indistinguishable growth
characteristics on primary porcine macrophage cell cultures. In vivo,
8-DR had no obvious effect on viral virulence in domestic pigs; disease onset, disease course, and mortality were similar for the
mutant
8-DR, its revertant 8-DR.R, and the parental virus. Altered
viral infection was, however, observed for pigs infected with
8-DR.
A delay in spread to and/or replication of
8-DR in the draining
lymph node, a delay in generalization of infection, and a 100- to
1,000-fold reduction in virus titers in lymphoid tissue and bone marrow
were observed. Onset of viremia for
8-DR-infected animals was
significantly delayed (by 2 to 5 days), and mean viremia titers were
reduced approximately 10,000-fold at 5 days postinfection and 30- to
100-fold at later times; moreover, unlike in 8-DR.R-infected animals,
the viremia was no longer predominantly erythrocyte associated but
rather was equally distributed among erythrocyte, leukocyte, and plasma
fractions. Mitogen-dependent lymphocyte proliferation of swine
peripheral blood mononuclear cells in vitro was reduced by 90 to 95%
following infection with 8-DR.R but remained unaltered following
infection with
8-DR, suggesting that 8-DR has
immunosuppressive activity in vitro. Together, these results suggest an
immunosuppressive role for 8-DR in the swine host which
facilitates early events in viral infection. This may be of most
significance for ASFV infection of its highly adapted natural host, the
warthog.
*
Corresponding author. Mailing address: Plum Island
Animal Disease Center, P.O. Box 848, Greenport, NY 11944-0848. Phone:
(516) 323-2500, ext. 330. Fax: (516) 323-2507.
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