Biological consequences of human cytomegalovirus IE1 and IE2 expression in rat cells.

摘要

We were interested in identifying functions of the HCMV IE gene products that are shared with the adenovirus E1a gene products. We investigated the ability of the HCMV immediate early one (IE1) and two (IE2) gene products to form dense foci in both primary rat embryo fibroblasts (REFs) and Rat2 cells, either by themselves or in cooperation with other known transforming oncogenes, such as the activated c-H-ras oncogenes and the mouse mutant p53 (mmp53) cellular gene. We were unable to detect any ability of the HCMV IE genes to form dense foci in these cell types either by themselves or in cooperation with either ras or mmp53. To the contrary, we found that these HCMV IE genes abrogated transformation mediated by the mmp53 plus ras genes and also by the adenovirus E1a plus ras genes in primary REFs. Analysis of cell lines developed from surviving colonies indicated that although IE DNA was present in some of the cell lines, the levels of IE proteins were below our limits of detection.;We wished to determine if the HCMV IE gene products shared the ability of the adenovirus E1a gene products to disrupt cellular actin cables. By infecting primary REFs with adenovirus-HCMV recombinant viruses expressing the HCMV IE1 and/or IE2 proteins or transfecting REFs with IE DNA constructs we demonstrated that the HCMV IE1 and IE2 gene products could disrupt actin cables. The observed disruption was determined by statistical analysis to be significant.;This study revealed two previously unidentified functions of the HCMV IE gene products. The ability of the IE products to disrupt cellular actin cables provides a second function that the IE products share with the adenovirus E1a gene products. The ability to abrogate transformation is not known to be a function of the adenovirus E1a gene products. Future studies will examine possible activities of the HCMV IE gene products that may be involved in these functions.