CHARACTERIZATION OF THE REGULATORY FUNCTION OF THE ICP22 PROTEIN OF EQUINE HERPESVIRUS TYPE-1

The IR4 gene (inverted repeat gene 4) of equine herpesvirus type 1 (EH V-), the homolog of the herpes simplex virus type 1 ICP22 gene, is dif ferentially expressed as a 1.4-kb early transcript and a 1.7-kb late t ranscript that encode a series of proteins that migrate between 42 to 47 kDa, localize to the nucleus of EHV-1-infected cells, and become pa ckaged within EHV-1 virions (V. R. Holden, G. B. Caughman, Y. Zhao, R. N. Harty, and D. J. O'Callaghan, J. Virol. 68, 4329-4340, 1994). To a ssess the role of the IR4 protein in EHV-1 gene regulation, an IR4 exp ression vector was cotransfected with EHV-1 chimeric promoter-CAT repo rter constructs and EHV-1 effector plasmids to determine the effects o f the IR4 protein on the expression of immediate-early (IE), early, an d late promoters. These studies revealed that the IR4 protein: (i) min imally trans-activates EHV-1 promoters, (ii) acts synergistically with the UL3 (ICP27) gene product to trans-activate the IE promoter, (iii) does not interfere with the trans-repression of the IE promoter by th e IE protein, (iv) enhances transactivation of early promoters by the IE protein, (v) enhances the transactivation of both early and late pr omoters by the IE and UL3 proteins, and (vi) interacts synergistically with the IE protein to trans-activate the heterologous HSV-1 ICP4 pro moter. These data suggest that the IR4 gene product plays a significan t role in EHV-1 gene regulation. (C) 1995 Academic Press, Inc.