Inhibition of cytomegalovirus immediate early gene expression: a therapeutic option?

• Published in: Antiviral Research 2001-03, Vol.49 (3), p.129-145
• Main Authors: Scholz, Martin, Doerr, Hans Wilhelm, Cinatl, Jindrich
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Antiviral therapy; Biological and medical sciences; Cytomegalovirus; Cytomegalovirus - drug effects; Cytomegalovirus - genetics; Cytomegalovirus - growth & development; Cytomegalovirus Infections - drug therapy; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Viral - drug effects; Genes, Immediate-Early - drug effects; Human cytomegalovirus; Humans; IE1 gene; IE2 gene; Immediate early gene expression; Immediate-Early Proteins - antagonists & inhibitors; Immediate-Early Proteins - biosynthesis; Immediate-Early Proteins - genetics; Immunocompromised Host; Immunopathomechanisms; Medical sciences; Microbiology; Pharmacology. Drug treatments; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Thionucleotides - pharmacology; Thionucleotides - therapeutic use; Virology
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/S0166-3542(01)00126-7

The replication cycle of the human cytomegalovirus (HCMV) is characterized by the expression of immediate early (IE), early (E), and late (L) gene regions. Current antiviral strategies are directed against the viral DNA polymerase expressed during the early phase of infection. The regulation of the IE-1 and IE-2 gene expression is the key to latency and active replication due to their transactivating and repressing functions. There is growing evidence that the pathogenic features of HCMV are largely due to the abilities of IE-1 and IE-2 to transactivate cellular genes. Consequently, current drugs used to inhibit HCMV infection would have no impact on IE-1 and IE-2-induced effects that are produced before the early phase. Moreover, when HCMV DNA replication is inhibited, IE gene products accumulate in infected cells causing disturbances of host cell functions. This review summarizes the biological functions of HCMV-IE gene expression, their relevance in pathogenesis, as well as efforts to develop novel treatment strategies directed against HCMV-IE expression.