Poster Sessions

V -6

Malen Link

M. Link, C. Sauder, C. Zhang, P. Duprex, K. Carbone, S. Rubin

Investigation of the Contribution of the Surface and Matrix Proteins of Mumps Virus Strain Urabe AM9 to Neurovirulence.

Prior to the introduction of live-attenuated vaccines, mumps virus was the leading cause of virus-induced meningitis. Unfortunately, some mumps vaccines, such as Urabe AM9 (Ur), have retained some neurovirulent properties and have caused aseptic meningitis in vaccinees. It is essential, therefore, to identify markers of mumps virus attenuation. However, the mechanism for viral neuroattenuation is not clearly understood. Furthermore, changes in neurovirulence have been associated by sequence analysis with mutations in almost every mumps virus gene. Therefore, genes that are important for neurovirulence are unlikely to be the same for each virus strain. To elucidate the contribution of defined genes of the Ur vaccine strain to neurotoxicity, we constructed chimeric full length infectious c-DNA clones of Ur and of the non-neurovirulent vaccine strain Jeryl Lynn (JL). We show that replacing combinations of the Ur genes encoding the membrane associated proteins M, F, SH, and HN with the corresponding genes from JL results in changes in growth kinetics in Vero cell culture. Notably, replacement of the combination of Ur proteins M, F, SH, and HN with the corresponding genes from JL results in a complete reduction of its neurovirulent potential in a neonatal rat model of neurovirulence.