Transcriptional analysis of the murine cytomegalovirus HindIII-I region: Identification of a novel immediate-early gene region

Cytomegaloviruses likely encode numerous gene products involved in regulati ng virus-host cell interactions and pathogenesis. We previously identified a region of murine cytomegalovirus (MCMV) within HindIII-J and -I that regu lates pathogenesis of the virus [open reading frames (ORFs) M139-M141] or i s likely required for MCMV replication (ORFs m142 and m143). As a prerequis ite for further studies on the structure and function of this gene region, we mapped the transcripts encoded within MCMV HindIII-I. Probes for ORFs M1 40 and M141 hybridized to 5.4- and 7.0-kb RNA, respectively, which were tra nscribed with early kinetics and were 3' coterminal with HindIII-J ORF M139 . Probes representing ORFs m142, m143, or m144 hybridized to 3' coterminal transcripts of 1.8, 3.8, and 5.1 kb, respectively. ORFs m142 and m143 were transcribed with immediate-early kinetics but were most abundantly expresse d at early times. Probes for the rightmost end of HindIII-I hybridized to a 5.1-kb early/late RNA corresponding to m144 and to a 1.8-kb early RNA tran scribed from m145. All of the major transcripts were polyadenylated and the refore are likely coding. Additional minor transcripts of intermediate size s were also detected. ORFs M139-m143 showed homology to the betaherpesvirus -specific HCMV US22 gene family. Because deletion of these viral genes resu lts in attenuated or helper-dependent phenotypes, this conserved region of US22 family genes may have a role in virus replication as well as in the pa thogenesis of betaherpesviruses in their natural hosts. (C) 1999 Academic P ress.