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Faculty Carol A. Wu
Assistant Professor of Immunology
cawu@nso1.uchc.edu
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
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