Objectives
Severe acute
respiratory syndrome (SARS) is a newly emerging global disease of humans
with a major economic impact and significant bioterrorism potential caused
by a new strain of coronavirus (CoV). The lung is the target organ related
to the disease manifestations, although diarrhea occurs in some patients.
Unresolved questions related to SARS pathogenesis include the mechanisms for
"superspreaders" and the atypical pneumonia and variable diarrhea induced
and the role of polymicrobial infections in the variable severity of SARS.
Host immune factors, especially proinflammatory cytokines may play a role in
the severe pulmonary damage, as observed in our studies of respiratory
disease in pigs. The widespread use of steroids and IFNs for treatment of
SARS patients without a clear understanding of their impact on respiratory
disease, necessitates studies of their impact in an animal model
susceptible to respiratory CoV infection. The anatomy, physiology and immune system of the
pig respiratory tract closely resembles that of man and pigs mimic humans in
the clinico-pathological manifestations of CoV or influenza infections, providing a unique
animal model for the study of viral respiratory disease of humans. The
porcine respiratory CoV (PRCV), a spike deletion mutant of the enteric CoV
transmissible gastroenteritis virus (TGEV), shows striking pathogenetic
similarities to SARS CoV in its primary replication in lung. Of interest,
PRCV invariably induces similar lung lesions with atypical pneumonia, even
in asymptomatic pigs. Our studies suggest that polymicrobial co-infections
influence the severity of PRCV infection, lesions and disease via multiple
mechanisms. These include the repertoire of proinflammatory cytokines or the
cell infiltrates induced in lung, and the multiple cell types infected.
Therefore our aim is to determine the influence of steroids and coinfections
with respiratory viruses or bacterial derived components (and the cytokines
induced) on the severity of a SARS-like respiratory coronavirus (PRCV)
infection of swine.
