|Derscheid, Rachel -|
|Van Geelen, A -|
|Gallup, Jack -|
|Cihlar, Tomas -|
|Ackermann, Mark -|
Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 20, 2013
Publication Date: November 22, 2013
Citation: Derscheid, R.J., van Geelen, A., McGill, J.L., Gallup, J.M., Cihlar, T., Sacco, R.E., Ackermann, M.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(11):2881-2897. DOI: 10.3390/v5112881. Interpretive Summary: Respiratory syncytial virus (RSV) is a virus that is present worldwide, causing a range of respiratory disease. There are both human and ruminant versions of the virus that cause very similar diseases in their respective host species; particularly similar in younger calves and lambs. Animal models in mice have proven insufficient for developing vaccines for use in humans or ruminants. Here a team of scientists developed a disease model in lambs that closely mimics the natural disease in ruminants or humans. This model may prove valuable for scientists and vaccine companies conducting efficacy and safety testing of vaccines for use in ruminants and potentially humans.
Technical 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.