Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression

• Published in: FEMS microbiology reviews Vol. 28; no. 1; pp. 59 - 77
• Main Authors: Cinatl, Jindrich, Vogel, Jens-Uwe, Kotchetkov, Rouslan, Wilhelm Doerr, Hans
• Format: Journal Article
• Language: English
• Published: Oxford, UK Elsevier B.V 01-02-2004; Blackwell Publishing Ltd; Blackwell; Oxford University Press
• Subjects: Adenoviruses; Angiogenesis; Antigen (tumor-associated); Antigens; Apoptosis; Biological and medical sciences; Cell Cycle; Cell proliferation; Cell survival; Cytomegalovirus; Cytomegalovirus - physiology; Cytomegalovirus Infections - pathology; Cytomegalovirus Infections - physiopathology; Cytomegalovirus Infections - virology; Deoxyribonucleic acid; DNA; DNA tumor viruses; DNA viruses; DNA-virus; Fundamental and applied biological sciences. Psychology; Genomes; Human cytomegalovirus; Human papillomavirus; Humans; Immunogenicity; Infections; Microbiology; Neoplasms - pathology; Neoplasms - physiopathology; Neoplasms - virology; Oncomodulation; Phenotypes; Proteins; Regulatory proteins; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Signal transduction; Signaling; Tumor; Tumor cell lines; Tumor cells; Tumors; Viral infections; Virology; Viruses; Angiogenesis; Tumor; Oncomodulation; Human cytomegalovirus; DNA-virus; Apoptosis; Induction; Herpesviridae; Betaherpesvirinae; Protein; Infection; Virus; Cell death; Viral disease; Cell cycle; DNA virus
• ISSN: 0168-6445; 1574-6976; 1574-6976
• DOI: 10.1016/j.femsre.2003.07.005

A high frequency of human cytomegalovirus (HCMV) genome and antigens in tumor samples of patients with different malignancies is now well documented, although the causative role for HCMV in the development of the neoplasias remains to be established. HCMV infection can modulate multiple cellular regulatory and signalling pathways in a manner similar to that of oncoproteins of small DNA tumor viruses such as human papilloma virus or adenoviruses. However, in contrast to these DNA tumor viruses, HCMV infection fails to transform susceptible normal human cells. There is now growing evidence that tumor cells with disrupted regulatory and signalling pathways enable HCMV to modulate their properties including stimulation of cell proliferation, survival, invasion, production of angiogenic factors, and immunogenic properties. In contrast to previously suggested “hit and run” transformation we suggest that persistence in tumor cells is essential for HCMV to fully express its oncomodulatory effects. These effects are observed particularly in persistent HCMV infection and are mediated mainly by activity of HCMV regulatory proteins. In persistently HCMV-infected tumor cell lines – a selection of novel, slowly growing virus variants with changes in coding sequences for virus regulatory proteins takes place. As a result, oncomodulatory effects of HCMV infection may lead to a shift to more malignant phenotype of tumor cells contributing to tumor progression.