Table 2.
Overlap of Human Cytomegalovirus (HCMV) biology with altered cellular physiologies classified as hallmarks of cancer
| Cancer Hallmark | HCMV Activity | HCMV Protein Involved |
|---|---|---|
| Sustaining Proliferative Signaling | Induces cell cycle progression to S phase | IE2 |
| Induces expression of E2F genes | pp71 | |
| Phosphorylates Rb | UL97 | |
| Evading Growth Suppressors | Activates EGFR | HCMV infection |
| Dysregulates Cyclin E expression | IE1 | |
| Inhibits p53 degradation | mtrII | |
| Decreases levels of p21 | ||
| Induces expression of p53 | ||
| Binds to p53 | ||
| Activating Invasion and Metastasis | Activation of RhoA dependent motility of U373 cells | US28 |
| Activates smooth muscle cells | ||
| Enabling Replicative Immortality | Activation of telomerase | IE1 |
| Inducing Angiogenesis | Induction of VEGF expression | US28 |
| Induction of IL-8 | IE1 | |
| Resisting Cell Death | Inhibits apoptosis | IE1 |
| Activates PI3-K/Akt pathway | IE2 vMIA, vICA | |
| Deregulating Cellular Energetics | Increases flux through glycolytic pathway, | HCMV infection |
| acetyl CoA, flux of carbon, nucleotide biosynthesis | ||
| Avoiding Immune Destruction | Production of homologs to immunosuppressive cytokines | HCMV IL-10 |
| Inhibits expression of MCH I | US2 | |
| Intracellular retention of NKG2D | UL16 | |
| Induces expression of TGF-β1 | IE2 | |
| Genome Instability and Mutation | Chromosome damage | Unidentified protein |
| Inhibits DNA damage repair | HCMV infection | |
| Increases mutation frequency | pp65 and pp71 | |
| Induces chromosome aberrations in cell lines | IE1 | |
| UL76 | ||
| Tumor Promoting Inflammation | Induces production of RANTES, fraktalkine, MCP-1 | HCMV infection |
| NF-κB activation & IL-6 production | US28 |