Saturday, February 5, 2011

More Barriers in RSV Research

The mechanism of respiratory syncytial virus (RSV) is poorly understood. Data on RSV pathogenesis is predominately derived using a laboratory-adapted prototypic strain, RSV strain A2. At the Queen's University Belfast, Villenave and colleagues challenge the use of RSV strain A2 and provide evidence that this strain is a poor in vitro representative of an actual in vivo infection.

Villenave et al. used primary pediatric bronchial epithelial cells (PBECs) to address how clinically representative or relevant the laboratory strain is relative to recent clinical isolates (designated RSV BT2a, BT3a, BT4a).

As opposed to the crippled laboratory E. coli, which has lost its ability to thrive in the intestine or form biofims after domestication, we find the opposite phenomenon: the A2 strain infected PBECs more efficiently than any of the clinical isolates with increased cytopathic effects. Cells infected with A2 had large syncytia formation, increased rounding, and extensive monolayer disruption compared to the isolates. RSV isolates had a limited capacity to infect PBECs and grew slowly with a low titer. They went on to test chemokine and cytokine secretions induced upon infection. Again, infection with A2 had a dramatically increased secretion of interferon-inducible protein 10 (IP-10/CXCL10), normal T cell expressed and secreted (RANTES/CCL5), interleukin 6 (IL-6) and IL-8 (CXCL8).

In attempt to explain this phenomenon, they serially passed the RSVs through passage 14. Even then, there was no data to support differential growth kinetics or cytopathogensis between A2 and the isolates. Because of the widespread usage of RSV A2 is pathogenicity studies for RSV infection, it may be a wise investment to find clinically relevant in vitro models.

Remi Villenave, Dara O'Donoghue, Surendran Thavagnanam, Olivier Touzelet, Grzegorz Skibinski, Liam G Heaney, James P McKaigue, Peter V Coyle, Michael D Shields and Ultan F Power. Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells. Virology Journal 2011, 8:43 doi:10.1186/1743-422X-8-43


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