A tumor-specific endogenous repetitive element is induced by herpesviruses

Abstract

Tandem satellite repeats account for 3% of the human genome. One of them, Human Satellite II (HSATII), is highly expressed in several epithelial cancers and cancer cell lines. Here we report an acute induction of HSATII RNA in human cells infected with two herpes viruses. We show that human cytomegalovirus (HCMV) IE1 and IE2 proteins cooperate to induce HSATII RNA affecting several aspects of the HCMV replication cycle, viral titers and infected-cell processes. HSATII RNA expression in tissue from two chronic HCMV colitis patients correlates with the strength of CMV antigen staining. Thus, endogenous HSATII RNA synthesis after herpesvirus infections appears to have functionally important consequences for viral replication and may provide a novel insight into viral pathogenesis. The HSATII induction seen in both infected and cancer cells suggests possible convergence upon common HSATII-based regulatory mechanisms in these seemingly disparate diseases.

P53 and The Immune Response: 40 Years of Exploration—A Plan for the Future

“…These high CpG content RNAs get packaged into exosomes and are shipped out of the cancer cells where they are then phagocytized by macrophages and dendritic cells. In macrophages and dendritic cells, the RNAs induce interferon, IL-6, and TNF from the innate immune system [34]. Thus, in any situation, like cancer, that results in the expression of high CpG repetitive DNA elements, these RNAs can trigger an innate immune response.…”

“…Interestingly, the very same set of events happens in some virus-infected cells when the virus inactivates p53 functions. [34]. In Cytomegalovirus and Herpes simplex types 1-and 2-infected cells, HSAT-2 is induced to transcribe its CpG rich sequences after infection.…”

“…For CMV, this is the cell type in which it becomes latent and remains in the body over a lifetime. For HSV-1 and -2, this should result in antigen presentation to adaptive immune responsive cells, and ultimate clearance of the virus until reactivation [34].…”

P2Y2 purinergic receptor modulates virus yield, calcium homeostasis, and cell motility in human cytomegalovirus-infected cells

“…Members of the Purinergic Receptor Network. To investigate the differential expression of cellular genes during infection, we analyzed our recently published dataset (46) derived by whole RNA sequencing of MRC-5 fibroblasts that were mock-infected or infected with the wild-type AD169 laboratory strain of HCMV (ADwt; 3 TCID 50 per cell). RNA was analyzed at 48 h postinfection (hpi), allowing us to monitor RNAs during the earlylate phase of the viral replication cycle (the late phase begins with the onset of viral DNA replication at 24 to 30 hpi; maximal yield of progeny is achieved at about 96 hpi).…”

“…To test this hypothesis, we focused on the viral IE1 and IE2 proteins, which are known to be promiscuous transcriptional activators (47,48). MRC5 fibroblasts were engineered to contain tetracycline-inducible GFP, IE1, IE2, or IE1+IE2 cDNAs (46). Only IE1-expressing cells (MRC5-IE1) were characterized by a strong induction of P2Y2 transcripts at 72 and 96 h postdoxycycline treatment ( Fig.…”