title: Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells.
abstract: Our previous studies showed that bovine respiratory syncytial virus (BRSV) followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2) epithelial cells with H. somni concentrated culture supernatant (CCS) stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2--RSAD2) and ISG15 (IFN-stimulated gene 15--ubiquitin-like modifier) were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT) upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide) but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt) does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo.
authors: Department of Pathology, University of California San Diego, San Diego, CA, United States of America.
authors: C
authors: C
authors: Lin
authors: Department of Pathology, University of California San Diego, San Diego, CA, United States of America.
authors: J T
authors: JT
authors: Agnes
authors: Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America.
authors: N
authors: N
authors: Behrens
authors: Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America.
authors: M
authors: M
authors: Shao
authors: Bacterial and Parasitic Diseases Research Division, National Institute of Animal Health, NARO, Tsukuba, Ibaraki, Japan.
authors: Y
authors: Y
authors: Tagawa
authors: Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America.
authors: L J
authors: LJ
authors: Gershwin
authors: Department of Pathology, University of California San Diego, San Diego, CA, United States of America.|Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America.
authors: L B
authors: LB
authors: Corbeil
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D001422:Bacterial Adhesion; D002417:Cattle; D002478:Cells, Cultured; D006192:Haemophilus Infections / Q000150:complications / Q000382:microbiology / Q000821:virology; D044138:Haemophilus somnus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000382:microbiology* / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000382:microbiology / Q000821:virology; D018112:Respiratory Syncytial Virus, Bovine / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D015854:Up-Regulation; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D011506:Proteins; D037521:Virulence Factors