title: Effects of rhinovirus species on viral replication and cytokine production.
abstract: BACKGROUND
  Epidemiologic studies provide evidence of differential virulence of rhinovirus species (RV). We recently reported that RV-A and RV-C induced more severe illnesses than RV-B, which suggests that the biology of RV-B might be different from RV-A or RV-C.
  
  
  OBJECTIVE
  To test the hypothesis that RV-B has lower replication and induces lesser cytokine responses than RV-A or RV-C.
  
  
  METHODS
  We cloned full-length cDNA of RV-A16, A36, B52, B72, C2, C15, and C41 from clinical samples and grew clinical isolates of RV-A7 and RV-B6 in cultured cells. Sinus epithelial cells were differentiated at the air-liquid interface. We tested for differences in viral replication in epithelial cells after infection with purified viruses (10(8) RNA copies) and measured virus load by quantitative RT-PCR. We measured lactate dehydrogenase (LDH) concentration as a marker of cellular cytotoxicity, and cytokine and/or chemokine secretion by multiplex ELISA.
  
  
  RESULTS
  At 24 hours after infection, the virus load of RV-B (RV-B52, RV-B72, or RV-B6) in adherent cells was lower than that of RV-A or RV-C. The growth kinetics of infection indicated that RV-B types replicate more slowly. Furthermore, RV-B released less LDH than RV-A or RV-C, and induced lower levels of cytokines and chemokines such as CXCL10, even after correction for viral replication. RV-B replicates to lower levels also in primary bronchial epithelial cells.
  
  
  CONCLUSIONS
  Our results indicate that RV-B types have lower and slower replication, and lower cellular cytotoxicity and cytokine and/or chemokine production compared with RV-A or RV-C. These characteristics may contribute to reduced severity of illnesses that has been observed with RV-B infections.
authors.affiliation: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakagome
authors.affiliation: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis.
authors.forename: Yury A
authors.initials: YA
authors.lastname: Bochkov
authors.affiliation: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis.
authors.forename: Shamaila
authors.initials: S
authors.lastname: Ashraf
authors.affiliation: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Brockman-Schneider
authors.affiliation: Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Evans
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, Wis.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pasic
authors.affiliation: Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis; Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wis. Electronic address: Gern@medicine.wisc.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
mesh_terms: D001249:Asthma / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000821:virology; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000821:virology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010850:Picornaviridae Infections / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000821:virology; D012229:Rhinovirus / Q000302:isolation & purification / Q000502:physiology*; D012720:Severity of Illness Index; D013045:Species Specificity; D019562:Viral Load; D014779:Virus Replication
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007770:L-Lactate Dehydrogenase
keywords: Asthma; cellular cytotoxicity; chemokine; cytokine; rhinovirus