Human cytomagalovirus IE1 and IE2 proteins are mutagenic and mediate "hit-and-run" oncogenic transformation in cooperation with the adenovirus E1A proteins.
Some epidemiological studies have suggested a possible link between human cytomegalovirus (HCMV) infection and various malignancies, and HCMV has been shown to transform cultured cells. However, viral DNA is not detected in most transformants, and the mechanism by which HCMV might contribute to oncogenesis has remained obscure. Here we show that the HCMV immediate early 1 and 2 genes can cooperate with the adenovirus E1A gene to generate transformed foci of primary baby rat kidney cells. HCMV gene expression is transient and viral DNA is not present in clonal cell lines derived from the transformed foci. We find that the HCMV immediate early proteins are mutagenic, and we propose that HCMV has the potential to contribute to oncogenesis through a "hit-and-run" mechanism, by inducing mutations in cellular genes.
Shen
Y
Y
Department of Molecular Biology, Princeton University, NJ 08544-1014, USA.
Zhu
H
H
Shenk
T
T
D017500:Adenovirus E1A Proteins / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D006224:Cricetinae; D017874:Immediate-Early Proteins / Q000502:physiology*; D008562:Membrane Glycoproteins; D016296:Mutagenesis; D051381:Rats; D015534:Trans-Activators; D014759:Viral Envelope Proteins; D014764:Viral Proteins
D017500:Adenovirus E1A Proteins; C088645:IE1 protein, cytomegalovirus; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D015534:Trans-Activators; C077406:UL115 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus