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Human Respiratory Syncytial Virus Memphis 37 Grown in HEp-2 Cells Causes more Severe Disease in Lambs than Virus Grown in Vero Cells
Department of Veterinary Pathology Iowa State University College of Veterinary Medicine, 1600 S. 16th St., Ames, IA 50011-1250, USA
Ruminant Diseases and Immunology Research Unit, National Animal Disease Center/USDA/ARS 1920 Dayton Ave., Ames, IA 50010, USA
Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA
* Authors to whom correspondence should be addressed.
Received: 14 November 2013; in revised form: 18 November 2013 / Accepted: 18 November 2013 / Published: 22 November 2013
Abstract: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants and young children. A small percentage of these individuals develop severe and even fatal disease. To better understand the pathogenesis of severe disease and develop therapies unique to the less-developed infant immune system, a model of infant disease is needed. The neonatal lamb pulmonary development and physiology is similar to that of infants, and sheep are susceptible to ovine, bovine, or human strains of RSV. RSV grown in Vero (African green monkey) cells has a truncated attachment G glycoprotein as compared to that grown in HEp-2 cells. We hypothesized that the virus grown in HEp-2 cells would cause more severe clinical symptoms and cause more severe pathology. To confirm the hypothesis, lambs were inoculated simultaneously by two different delivery methods (intranasal and nebulized inoculation) with either Vero-grown or HEp-2-grown RSV Memphis 37 (M37) strain of virus to compare viral infection and disease symptoms. Lambs infected with HEp-2 cell-derived virus by either intranasal or nebulization inoculation had significantly higher levels of viral RNA in lungs as well as greater clinical disease including both gross and histopathologic lesions compared to lambs similarly inoculated with Vero-grown virus. Thus, our results provide convincing in vivo evidence for differences in viral infectivity that corroborate previous in vitro mechanistic studies demonstrating differences in the G glycoprotein expression by RSV grown in Vero cells.
Keywords: G protein; HEp-2; Infant; lamb; lung; respiratory syncytial virus (RSV); Vero
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Derscheid, R.J.; van Geelen, A.; McGill, J.L.; Gallup, J.M.; Cihlar, T.; Sacco, R.E.; Ackermann, M.R. Human Respiratory Syncytial Virus Memphis 37 Grown in HEp-2 Cells Causes more Severe Disease in Lambs than Virus Grown in Vero Cells. Viruses 2013, 5, 2881-2897.
Derscheid RJ, van Geelen A, McGill JL, Gallup JM, Cihlar T, Sacco RE, Ackermann MR. Human Respiratory Syncytial Virus Memphis 37 Grown in HEp-2 Cells Causes more Severe Disease in Lambs than Virus Grown in Vero Cells. Viruses. 2013; 5(11):2881-2897.
Derscheid, Rachel J.; van Geelen, Albert; McGill, Jodi L.; Gallup, Jack M.; Cihlar, Tomas; Sacco, Randy E.; Ackermann, Mark R. 2013. "Human Respiratory Syncytial Virus Memphis 37 Grown in HEp-2 Cells Causes more Severe Disease in Lambs than Virus Grown in Vero Cells." Viruses 5, no. 11: 2881-2897.