Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II

Autoři: Ming Li aff001;  Christopher B. Ball aff002;  Geoffrey Collins aff002;  Qiaolin Hu aff001;  Donal S. Luse aff003;  David H. Price aff002;  Jeffery L. Meier aff001
Působiště autorů: Departments of Internal Medicine and Epidemiology, University of Iowa and Iowa City Veterans Affairs Health Care System, Iowa City, IA, United States of America aff001;  Department of Biochemistry, University of Iowa, Iowa City, IA, United States of America aff002;  Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America aff003
Vyšlo v časopise: Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II. PLoS Pathog 16(4): e1008402. doi:10.1371/journal.ppat.1008402
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008402


Herpesvirus late promoters activate gene expression after viral DNA synthesis has begun. Alphaherpesviruses utilize a viral immediate-early protein to do this, whereas beta- and gammaherpesviruses primarily use a 6-member set of viral late-acting transcription factors (LTF) that are drawn to a TATT sequence in the late promoter. The betaherpesvirus, human cytomegalovirus (HCMV), produces three immediate-early 2 protein isoforms, IE2-86, IE2-60, IE2-40, late in infection, but whether they activate late viral promoters is unknown. Here, we quickly degrade the IE2 proteins in late infection using dTag methodology and analyze effects on transcription using customized PRO-Seq and computational methods combined with multiple validation methods. We discover that the IE2 proteins selectively drive RNA Pol II transcription initiation at a subset of viral early-late and late promoters common to different HCMV strains, but do not substantially affect Pol II transcription of the 9,942 expressed host genes. Most of the IE2-activated viral late infection promoters lack the TATT sequence bound by the HCMV UL87-encoded LTF. The HCMV TATT-binding protein is not mechanistically involved in late RNA expression from the IE2-activated TATT-less UL83 (pp65) promoter, as it is for the TATT-containing UL82 (pp71) promoter. While antecedent viral DNA synthesis is necessary for transcription from the late infection viral promoters, continued viral DNA synthesis is unnecessary. We conclude that in late infection the IE2 proteins target a distinct subset of HCMV early-late and late promoters for transcription initiation by RNA Pol II. Commencement of viral DNA replication renders the HCMV genome late promoters susceptible to late-acting viral transcription factors.

Klíčová slova:

Cytomegalovirus infection – DNA replication – DNA transcription – DNA-binding proteins – Human cytomegalovirus – Polymerase chain reaction – Transcription factors – Viral genomics


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