title: Respiratory syncytial virus (RSV) infection in elderly mice results in altered antiviral gene expression and enhanced pathology.
abstract: Elderly persons are more susceptible to RSV-induced pneumonia than young people, but the molecular mechanism underlying this susceptibility is not well understood. In this study, we used an aged mouse model of RSV-induced pneumonia to examine how aging alters the lung pathology, modulates antiviral gene expressions, and the production of inflammatory cytokines in response to RSV infection. Young (2-3 months) and aged (19-21 months) mice were intranasally infected with mucogenic or non-mucogenic RSV strains, lung histology was examined, and gene expression was analyzed. Upon infection with mucogenic strains of RSV, leukocyte infiltration in the airways was elevated and prolonged in aged mice compared to young mice. Minitab factorial analysis identified several antiviral genes that are influenced by age, infection, and a combination of both factors. The expression of five antiviral genes, including pro-inflammatory cytokines IL-1β and osteopontin (OPN), was altered by both age and infection, while age was associated with the expression of 15 antiviral genes. Both kinetics and magnitude of antiviral gene expression were diminished as a result of older age. In addition to delays in cytokine signaling and pattern recognition receptor induction, we found TLR7/8 signaling to be impaired in alveolar macrophages in aged mice. In vivo, induction of IL-1β and OPN were delayed but prolonged in aged mice upon RSV infection compared to young. In conclusion, this study demonstrates inherent differences in response to RSV infection in young vs. aged mice, accompanied by delayed antiviral gene induction and cytokine signaling.
authors.affiliation: Department of Internal Medicine, James A. Haley Veterans Affairs Hospital, Tampa, Florida, United States of America ; Division of Translational Medicine and Nanomedicine Research Center, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Terianne M
authors.initials: TM
authors.lastname: Wong
authors.affiliation: Department of Internal Medicine, James A. Haley Veterans Affairs Hospital, Tampa, Florida, United States of America ; Division of Translational Medicine and Nanomedicine Research Center, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Boyapalle
authors.affiliation: Division of Translational Medicine and Nanomedicine Research Center, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Viviana
authors.initials: V
authors.lastname: Sampayo
authors.affiliation: Division of Translational Medicine and Nanomedicine Research Center, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Huy D
authors.initials: HD
authors.lastname: Nguyen
authors.affiliation: Division of Translational Medicine and Nanomedicine Research Center, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Raminder
authors.initials: R
authors.lastname: Bedi
authors.affiliation: Division of Translational Medicine and Nanomedicine Research Center, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Siddharth G
authors.initials: SG
authors.lastname: Kamath
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, Georgia, United States of America ; Children's Healthcare of Atlanta, Atlanta, Georgia, United States of America.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
authors.affiliation: Department of Internal Medicine, James A. Haley Veterans Affairs Hospital, Tampa, Florida, United States of America ; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Subhra
authors.initials: S
authors.lastname: Mohapatra
authors.affiliation: Department of Internal Medicine, James A. Haley Veterans Affairs Hospital, Tampa, Florida, United States of America ; Division of Translational Medicine and Nanomedicine Research Center, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Mohapatra
mesh_terms: D000375:Aging; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000821:virology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D016207:Cytokines