Preliminary studies have revealed that herpes simplex viruses (HSV) induce major reorganization of the nuclear complement of small nuclear ribonucleoprotein complexes (snRNP), which are now recognized to be involved in the normal processing of cellular messenger RNA precursors (pre-mRNA). Viral infection causes the segregation of snRNP from other host cell pre-mRNP components, leading to the formation of large aggregates of snRNP associated with the interchromatin granule regions of the cell nucleus. The reorganization of host cell nuclear components appears to be the result of HSV early gene activity. Since only a minority of known HSV pre-mRNAs require splicing, the generally accepted function of snRNP, we suggest that the virus acts to shut off these host cell activities thereby gaining competitive advantage. It is therefore proposed to assay effects of HSV infection of mammalian cells on pre-mRNA processing by analyzing the fate of selected mRNA precursors, using nucleic acid probes specific for precursor and mature mRNA sequences. The involvement of HSV genes in the reorganization of the nucleus using mutant viruses and transfection with cloned viral DNA sequences will also be determined. The snRNP clusters will be isolated from infected cells, and characterized biochemically and immunologically with respect to both host cell and viral components. In addition to furthering knowledge of the metabolism of infected cells these studies may also indicate possible mechanisms for viral factors in cellular transformation and autoimmune disorders.

R01CA048189

1988-08-01

1992-07-31