Suzanne Barnard

Publications (2)6.73 Total impact

• Article: Mouse respiratory epithelial cells support efficient replication of human rhinovirus.

  Tobias J Tuthill, Nikolaos G Papadopoulos, Patrick Jourdan, Lisa J Challinor, Nigel A Sharp, Chris Plumpton, Ketaki Shah, Suzanne Barnard, Laura Dash, Jerome Burnet, Richard A Killington, David J Rowlands, Neil J Clarke, Edward D Blair, Sebastian L Johnston
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  ABSTRACT: Human rhinoviruses (HRV) are responsible for the majority of virus infections of the upper respiratory tract. Furthermore, HRV infection is associated with acute exacerbation of asthma and other chronic respiratory diseases of the lower respiratory tract. A small animal model of HRV-induced disease is required for the development of new therapies. However, existing mouse models of HRV infection are difficult to work with and until recently mouse cell lines were thought to be generally non-permissive for HRV replication in vitro. In this report we demonstrate that a virus of the minor receptor group, HRV1B, can infect and replicate in a mouse respiratory epithelial cell line (LA-4) more efficiently than in a mouse fibroblast cell line (L). The major receptor group virus HRV16 requires human intercellular adhesion molecule-1 (ICAM-1) for cell entry and therefore cannot infect LA-4 cells. However, transfection of in vitro-transcribed HRV16 RNA resulted in the replication of viral RNA and production of infectious virus. Expression of a chimeric ICAM-1 molecule, comprising mouse ICAM-1 with extracellular domains 1 and 2 replaced by the equivalent human domains, rendered the otherwise non-permissive mouse respiratory epithelial cell line susceptible to entry and efficient replication of HRV16. These observations suggest that the development of mouse models of respiratory tract infection by major as well as minor group HRV should be pursued.
  Journal of General Virology 11/2003; 84(Pt 10):2829-36. · 3.36 Impact Factor
• Article: Transcription mapping of human herpesvirus 8 genes encoding viral interferon regulatory factors.

  Charles Cunningham, Suzanne Barnard, David J Blackbourn, Andrew J Davison
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  ABSTRACT: The human herpesvirus 8 (HHV-8) genome contains four tandemly arranged genes encoding viral interferon regulatory factors (vIRF-1 to 4) located between genes 57 and 58. Transcript mapping techniques were employed to determine the sizes, ends and splicing patterns of mRNAs specified by these genes in HHV-8-infected cell lines untreated or chemically induced into the lytic growth cycle. Depending on the cell line used, vIRF-3 transcription was minimally or not induced (i.e. expressed with latent kinetics), whereas the other vIRFs were inducible (i.e. expressed with lytic kinetics). Each gene possessed its own promoter (or promoters) and polyadenylation sites, and all but vIRF-1 were spliced from two exons. vIRF-1 was transcribed in uninduced and induced cells from a single initiation site preceded by a TATA box, with the possible use of an additional TATA box and initiation site in uninduced cells. In induced cells, vIRF-2 was transcribed from a single major initiation site preceded by a TATA box, and vIRF-4 was expressed from two sites each preceded by a TATA box. Transcripts for these genes were insufficiently abundant in uninduced cells to map the 5'-ends. vIRF-3 lacks an obvious TATA box and exhibited heterogeneous 5'-ends in uninduced and induced cells. These data clarify and extend our understanding of the structure and transcription of the HHV-8 vIRF genes.
  Journal of General Virology 07/2003; 84(Pt 6):1471-83. · 3.36 Impact Factor