Role of the Human Cytomegalovirus Major Immediate-Early Promoter's 19-Base-Pair-Repeat Cyclic AMP-Response Element in Acutely Infected Cells
AUTOR(ES)
Keller, M. J.
FONTE
American Society for Microbiology
RESUMO
Prior studies have suggested a role of the five copies of the 19-bp-repeat cyclic AMP (cAMP)-response element (CRE) in major immediate-early (MIE) promoter activation, the rate-limiting step in human cytomegalovirus (HCMV) replication. We used two different HCMV genome modification strategies to test this hypothesis in acutely infected cells. We report the following: (i) the CREs do not govern basal levels of MIE promoter activity at a high or low multiplicity of infection (MOI) in human foreskin fibroblast (HFF)- or NTera2-derived neuronal cells; (ii) serum and virion components markedly increase MIE promoter-dependent transcription at a low multiplicity of infection (MOI), but this increase is not mediated by the CREs; (iii) forskolin stimulation of the cAMP signaling pathway induces a two- to threefold increase in MIE RNA levels in a CRE-specific manner at a low MOI in both HFF- and NTera2-derived neuronal cells; and (iv) the CREs do not regulate basal levels of HCMV DNA replication at a high or low MOI in HFF. Their presence does impart a forskolin-induced increase in viral DNA replication at a low MOI but only when basal levels of MIE promoter activity are experimentally diminished. In conclusion, the 19-bp-repeat CREs add to the robust MIE promoter activity that occurs in the acutely infected stimulated cells, although the CREs' greater role may be in other settings.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=156166Documentos Relacionados
- The promoter-regulatory region of the major immediate-early gene of human cytomegalovirus responds to T-lymphocyte stimulation and contains functional cyclic AMP-response elements.
- Human cytomegalovirus immediate-early two protein region involved in negative regulation of the major immediate-early promoter.
- The promoter of the human parathyroid hormone gene contains a functional cyclic AMP-response element.
- Role of the Proximal Enhancer of the Major Immediate-Early Promoter in Human Cytomegalovirus Replication
- Autoregulation of the human cytomegalovirus major immediate-early gene.