Differential expression of proinflammatory cytokine genes in vivo in response to pathogenic and nonpathogenic pneumovirus infections.
Pneumonia virus of mice (PVM; Paramyxoviridae, subfamily Pneumovirinae) is an important pathogen for the study of physiologically relevant acute inflammatory responses in rodent hosts. In contrast to the severe symptomatology observed in response to infection with PVM strain J3666, infection with strain 15 resulted in few clinical symptoms, limited cellular inflammatory response, and no production of macrophage inflammatory protein-1alpha or monocyte chemoattractant peptide (MCP)-1. Microarray analysis of transcripts from lung tissue indicates that PVM J3666 infection promotes up-regulation of specific proinflammatory genes, most notably interferon (IFN)-1beta, IFN response genes, and chemokines MCP-1, MCP-3, RANTES (regulated on activation, normally T cell-expressed and secreted), and eotaxin. Of these, only RANTES expression increased in response to infection with strain 15, with no increased expression of IFN or IFN response genes, despite ongoing viral replication. These results suggest that pneumovirus replication alone is insufficient to promote antiviral inflammation and that evaluation of the more divergent strain-specific pneumovirus proteins may provide some intriguing leads toward the molecular basis of this differential response.
Domachowske
Joseph B
JB
Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, NY 13210, USA. domachoj@upstate.edu
Bonville
Cynthia A
CA
Easton
Andrew J
AJ
Rosenberg
Helene F
HF
D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D018946:Chemokine CCL5 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D029122:Murine pneumonia virus; D020411:Oligonucleotide Array Sequence Analysis; D018186:Pneumovirus Infections / Q000276:immunology* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation; D014779:Virus Replication
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016207:Cytokines; D012333:RNA, Messenger; D016899:Interferon-beta