title: Functional and immune response to respiratory syncytial virus infection in aged BALB/c mice: a search for genes determining disease severity.
abstract: BACKGROUND
  Recent studies have demonstrated that respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in the elderly. The cellular mechanisms that determine the host's susceptibility and severity of the disease are not well understood. In this study, we sought a mouse model of human respiratory disease by studying the functional and cellular response to RSV in aged animals.
  
  
  METHODS
  Aged BALB/c mice (>10 months of age) were infected with human RSV (strain A2) and compared with sham-infected mice. Clinical progress of the illness was monitored by daily assessment of weight changes and mortality. The animals were sacrificed four days postinfection. Lung pathology was obtained and viral titers were measured by plaque assay. Gene expression profiles were studied from lung tissue RNA using gene array.
  
  
  RESULTS
  RSV produced significant clinical illness in aged mice as evidenced by a 15% weight loss and a 10% mortality rate. Lung pathology revealed inflammatory changes with a predominance of neutrophils and diffuse alveolar damage. Microarray analysis revealed variable profiles of gene activation/downregulation at day 4 postinfection. RSV infection resulted in a proinflammatory response. Surprisingly, some of the genes involved in antigen-processing pathway were downregulated, specifically, genes implicated in the major histocompatibility complex (MHC) class II pathway.
  
  
  CONCLUSIONS
  Our findings indicate that RSV infection produces profound functional and cellular changes in aged mice thus resembling the human disease described in the elderly. Further studies will be needed to understand the cellular mechanisms involved in the host response to RSV in aged mice.
authors.affiliation: University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Mosquera
authors.forename: James M
authors.initials: JM
authors.lastname: Stark
authors.forename: Constance L
authors.initials: CL
authors.lastname: Atkins
authors.forename: Guiseppe N
authors.initials: GN
authors.lastname: Colasurdo
authors.forename: Justyna
authors.initials: J
authors.lastname: Chevalier
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Samuels
authors.forename: Susan S
authors.initials: SS
authors.lastname: Pacheco
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D012720:Severity of Illness Index