Altered pathogenesis of severe pneumovirus infection in response to combined antiviral and specific immunomodulatory agents.
We report here the responses of mice with symptomatic pneumovirus infection to combined antiviral and specific immunomodulatory agents. Mice infected with pneumonia virus of mice, a natural mouse pathogen that replicates the signs and symptoms of severe infection with respiratory syncytial virus (RSV), responded to the antiviral agent ribavirin when it was administered in the setting of endogenous (gene deletion) or exogenous (antibody-mediated) blockade of the MIP-1alpha proinflammatory signaling cascade. Although neither treatment is effective alone, together they offer a dramatic reduction in symptoms and pathology, the most impressive of which is a significant reduction in morbidity and mortality. The findings presented are consistent with the notion of unique and independent contributions of virus replication and ongoing inflammation to the pathogenesis of severe respiratory virus infection, and they provide the impetus for the study of this treatment regimen in RSV-infected humans.
Bonville
Cynthia A
CA
Department of Pediatrics, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Easton
Andrew J
AJ
Rosenberg
Helene F
HF
Domachowske
Joseph B
JB
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000998:Antiviral Agents / Q000627:therapeutic use*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000096:biosynthesis; D017353:Gene Deletion; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D029122:Murine pneumonia virus / Q000472:pathogenicity* / Q000502:physiology; D011024:Pneumonia, Viral / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D012254:Ribavirin / Q000494:pharmacology; D014779:Virus Replication
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000998:Antiviral Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D012254:Ribavirin