We established earlier that a human neuroblastoma (NB) cell line grown in monolayer culture and treated with gamma-interferon and nerve growth factor induced long-lasting morphological and biochemical neuronal differentiation. This system was developed to serve as an in vitro model paralleling the infection of mature neurons by poliovirus in vivo. We found that, in contrast to the undifferentiated (i.e., untreated) NB cells, replication of the Sabin strain of attentuated poliovirus in the differentiated NB cells was suppressed and the selection of neurovirulent revertants significantly enhanced. Our latest data show that in monolayer cultures gamma-interferon inhibits the replication of poliovirus depending on the degree of it~s attenuation. Whereas the replication of the original vaccine virus was inhibited between 1.5 - 2.5 logs, the replication of a more neurovirulent vaccine-revertant strain was inhibited only between 1 - 1.5 logs. This suggests that our in vitro system can be used for discrimination between original and revertant vaccine strains. We now have preliminary data, using an in vitro technique developed in our laboratory, that gamma-interferon treated NB cells can distinguish between the vaccine virus and the neurovirulent revertant strains by a 1000 fold difference in their replication rates. Data on gamma-interferon and nerve growth factor induced NB differentiation were presented at the Keystone Symposia on Molecular and Cellular Biology in 1993. A manuscript is being revised for publication.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BR005002-06
Application #
3748321
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost