Respiratory dysfunction and proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis.
We explore relationships linking clinical symptoms, respiratory dysfunction, and local production of proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis. With a reduced inoculum of this natural rodent pathogen, we observe virus clearance by day 9, while clinical symptoms and respiratory dysfunction persist through days 14 and 17 postinoculation, respectively. Via microarray and ELISA, we identify expression profiles of proinflammatory mediators MIP-1alpha, MCP-1, and MIP-2 that correlate with persistent respiratory dysfunction. MIP-1alpha is localized in bronchial epithelium, which is also the major site of PVM replication. Interferon-gamma was detected in lung tissue, but at levels that do not correlate with respiratory dysfunction. Taken together, we present a modification of our pneumovirus infection model that results in improved survival and data that stand in support of a connection between local production of specific mediators and persistent respiratory dysfunction in the setting of acute viral bronchiolitis.
Bonville
Cynthia A
CA
SUNY Upstate Medical University, Syracuse, NY 13210-2375, USA.
Bennett
Nicholas J
NJ
Koehnlein
Melissa
M
Haines
Deborah M
DM
Ellis
John A
JA
DelVecchio
Alfred M
AM
Rosenberg
Helene F
HF
Domachowske
Joseph B
JB
D000818:Animals; D001990:Bronchiolitis, Viral / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D018932:Chemokine CCL2 / Q000032:analysis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000032:analysis; D008168:Lung / Q000473:pathology / Q000821:virology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D029122:Murine pneumonia virus; D020411:Oligonucleotide Array Sequence Analysis; D010993:Plethysmography, Whole Body; D018186:Pneumovirus Infections / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D015656:Respiratory Mechanics; D020545:Respiratory Mucosa / Q000737:chemistry
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma