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J. Virol., Feb 1996, 1109-1116, Vol 70, No. 2
ML Barkon, BL Haller and HW Virgin 4th
Reoviruses are encapsidated double-stranded RNA viruses that cause systemic
disease in mice after peroral (p.o.) inoculation and primary replication in
the intestine. In this study, we define components of the immune system
involved in the clearing of reovirus from the proximal small intestine. The
intestines of immunocompetent adult CB17, 129, and C57BL/6 mice were
cleared of reovirus serotype 3 clone 9 (T3C9) within 7 days of p.o.
inoculation. Antigen-specific lymphocytes were important for the clearance
of intestinal infection, since severe combined immunodeficient (SCID) mice
failed to clear T3C9 infection. To define specific immune components
required for intestinal clearance, reovirus infection of mice with null
mutations in the immunoglobulin M (IgM) transmembrane exon (MuMT; B cell
and antibody deficient) or beta 2 microglobulin gene (beta 2-/-; CD8
deficient) was evaluated. beta 2-/- mice cleared reovirus infection with
normal kinetics, while MuMT mice showed delayed clearance of T3C9 7 to 11
days after p.o. inoculation. Adoptive transfer of splenic lymphocytes from
reovirus-immune CB17 mice inhibited growth of T3C9 in CB17 SCID mouse
intestine 11 days after p.o. inoculation. The efficiency of viral clearance
by adoptively transferred cells was significantly diminished by depletion
of B cells prior to adoptive transfer. Results in SCID and MuMT mice
demonstrate an important role for B cells or IgG in clearance of reovirus
from the intestines. Polyclonal reovirus-immune rabbit serum, protein
A-purified immune IgG, and murine monoclonal IgG2a antibody specific for
reovirus outer capsid protein sigma 3 administered intraperitoneally all
normalized clearance of reovirus from intestinal tissue in MuMT mice. This
result demonstrates an IgA-independent role for IgG in the clearance of
intestinal virus infection. Polyclonal reovirus-immune serum also
significantly decreased reovirus titers in the intestines of SCID mice,
demonstrating a T-cell-independent role for antibody in the clearance of
intestinal reovirus infection. B cells and circulating IgG play an
important role in the clearance of reovirus from intestines, suggesting
that IgG may play a more prominent functional role at mucosal sites of
primary viral replication than was previously supposed.
Copyright © 1996, American Society for Microbiology
Circulating immunoglobulin G can play a critical role in clearance of intestinal reovirus infection
Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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