A. Phelan et al., A HERPES-SIMPLEX VIRUS TYPE-1 IMMEDIATE-EARLY GENE-PRODUCT, IE63, REGULATES SMALL NUCLEAR RIBONUCLEOPROTEIN DISTRIBUTION, Proceedings of the National Academy of Sciences of the United Statesof America, 90(19), 1993, pp. 9056-9060
Herpes simplex virus 1 (HSV-1), a nuclear replicating DNA virus, has 7
3 identified genes of which only 4 contain introns. For this reason th
e virus probably makes only minimal use of the cellular RNA-splicing m
achinery. Antigens associated with the small nuclear ribonucleoprotein
particles (snRNPs) that are subunits of splicing complexes have been
reported to redistribute in the nucleus and become concentrated into t
he intranuclear structures, the interchromatin granules, after HSV-1 i
nfection [Martin, T. E., Barghusen, S. C., Leser, G. P. & Spear, P. G.
(1987) J. Cell Biol. 105, 2069-2082]. We observe this snRNP redistrib
ution upon HSV-1 infection, in which the widespread snRNP staining pat
tern changes to a restricted punctate distribution with a concomitant
loss of coiled bodies in HSV-1-infected cells. We show here that expre
ssion of the immediate-early (IE) subset of HSV-1 genes is necessary a
nd sufficient for snRNP redistribution. Using a series of HSV-1 mutant
s in different IE genes, we have established that specifically the pro
duct of the viral IE63 (ICP27) gene is essential for this effect, and
transfection experiments revealed that IE63 expression alone can cause
the snRNP redistribution. Further, we show that the IE63 gene product
colocalizes with the redistributed snRNP in the nucleus. The snRNP re
distribution caused by HSV-1 infection resembles the effect seen after
inhibition of transcription in uninfected cells. In HSV-1-infected ce
lls, however, the snRNP redistribution is under the control of viral I
E gene products and occurs during active virus gene transcription.