IDENTIFICATION AND CHARACTERIZATION OF HUMAN CYTOMEGALOVIRUS/CELLULAR PROTEINS

Norfolk State University, Norfolk VA

Investigators

Linked publications & trials

Abstract

Human cytomegalovirus (HCMV) is a widespread opportunistic pathogen capable of establishing either a[unreadable] persistent or latent infection. In most cases, HCMV infection is benign or asymptomatic in healthy[unreadable] ndividuals. However, serious illness occurs upon infection in infants and immunocompromised adults. The[unreadable] genome is expressed in et temporally ordered manner and occurs in three separate phases: immediate early[unreadable] IE), early, and late. The early phase, which begins just prior to DNA replication, is further divided into three[unreadable] subclasses based on the expression level of early transcripts through the course of infection. /[unreadable] Studies on several HCMV early promoters have been undertaken to determine how HCMV early gene[unreadable] expression is regulated. Several specific DNA sequences as well as proteins have been identified. Some[unreadable] HCMV early promoter sequences are bound by HCMV specific proteins (IE86) as well as such as cellular[unreadable] proteins such as the cyclic AMP response element binding protein (CREB) or activated transcription factor[unreadable] [ATF). Activation of the early promoters requires the presence of IE86 and IE72 proteins or IE86 alone.[unreadable] *[unreadable] The UL98 early gene encodes a 58-65 kDa protein and is part of a family of nested 3' coterminal ORFs that[unreadable] share a polyadenylation site. The alkaline exonuclease plays a critical role in processing newly synthesized[unreadable] replicated copies of genome during maturation. We have determined that the HCMV UL98 promoter utilizes[unreadable] CRE and gamma (g) IRE to optimally regulate the expression of this early gene. In deletion analysis, a Tcell[unreadable] factor-like element (TCP) has also been implicated. Studies have also shown that the protein CREB[unreadable] interacts with the CRE sequences in gel mobility shift assays. However, the specific proteins associated[unreadable] with regulation through the TCF-1 and gIRE sites have yet to be characterized. Our objective in the following[unreadable] studies will be to identify the viral/cellular protein(s) that bind the TCF-1 element and gIRE. The analysis of[unreadable] regulatory mechanisms for this key viral early gene will provide insight into the overall regulation of early[unreadable] gene expression and the future development of novel antiviral therapies.