Areas of Interest
Epidemiologic evidence supports a close relationship between
respiratory viral infections and exacerbations of asthma.
However, the mechanisms by which viruses induce the onset of an
asthma attack or increase its severity are not fully understood,
and are likely to involve alterations in airway inflammation
through the activation of T lymphocytes and the subsequent
release of cytokines. The primary focus of our laboratory
centers on the influence of concomitant murine cytomegalovirus (MCMV)
infection, an opportunistic respiratory pathogen, on the
ovalbumin-induced (OVA) model of allergic airway disease.
The OVA-induced model of allergic airway disease mimics many
of the features observed in individuals with asthma including
airway eosinophilia, hyperreactivity to methacholine challenge,
and airway goblet cell hyperplasia often accompanied by
increased mucus production. We have demonstrated that
concomitant MCMV infection results in a decrease in the
synthesis of Th2 cytokines (IL-4, IL-5, and IL-13) and a
corresponding decline in airway eosinophilia. In addition,
concomitant MCMV infection increases epithelial cell
hypertrophy/hyperplasia, enhances mucus plugging, and increases
hyperreactivity to methacholine challenge. This increase in
mucus production makes concomitant MCMV infection a useful model
for studying the exacerbation of allergic airway disease. Our
hypothesis is that MCMV infection, which elicits a strong Th1
antiviral response, alters the balance of Th2 cytokines normally
associated with allergic airway disease. Indeed, decreased
levels of IL-5, a cytokine necessary for eosinophil recruitment,
are associated with decreased airway eosinophilia. In addition,
increased levels of IL-10 mRNA have been detected in the lungs
of concomitantly infected mice and IL-10 has been associated
with enhanced mucus production in the OVA-induced model. Taken
together, these findings suggest that MCMV infection can
effectively modulate the disease process and highlight the
complex nature of allergic airway disease with respect to
respiratory viral infections.
Selected References
Shanley, J.D., Carlson, M.E., and Wu, C.A. Mucosal immunization
with a replication-deficient adenovirus vector expressing murine
cytomegalovirus glycoprotein B induces mucosal and systemic
immunity. Vaccine, in press. 2003
Wu, C.A., Puddington, L., Whiteley, H.E., Yiamouyiannis,
C.A., Mohammadu, F., and Thrall, R.S. 2001. Murine
cytomegalovirus infection alters Th1/Th2 cytokine expression,
decreases airway eosinophilia, and enhances mucus production in
allergic airway disease. J. Immunol. 167, 2798-2807
Wu, C.A., Wu, Q., Henry, C., and Shanley, J.D. 1999. The
murine cytomegalovirus M25 open reading frame encodes a tegument
protein. Virology, 262, 265-276
Wu, C.A. and Shanley, J.D. 1998. Chronic infection of human
umbilical vein endothelial cells by human herpesvirus-6.
J.Gen.Viol. 79, 1247-1256 |
