The study identifies a nuclear RNA-modifying and -unwinding activity in human neuroblastoma cells that may be responsible for biased hypermutation of measles virus strains infecting the central nervous system.
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Nuclear dsRNA unwinding activity in neuroblastoma cells may drive CNS measles hypermutation; leaves open its role in viral persistence pending primary cell studies.
The matrix (M) gene of a measles virus (MV) variant passaged in IMR-32 human neuroblastoma cells displays numerous uridine-to-cytosine transitions called biased hypermutation. Using an in vitro assay, we show that IMR-32 cells contain high levels of an activity which unwinds and irreversibly alters the base pairing of double-stranded RNA synthesized from the M gene of MV. This activity is found exclusively in the cellular nucleus and is present at a lower level in African green monkey kidney Vero cells. Experiments with mixed cell extracts suggest that the low activity in Vero cells is not due to inhibitory factors. These findings support the hypothesis that this RNA-modifying and -unwinding activity is responsible for biased hypermutation of MV strains that infect the central nervous system. Possible functions of this neural cell activity and implications for central nervous system disorders are discussed.
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Rataul et al. (1992) studied this question.
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