TY - JOUR
T1 - A tumor-specific endogenous repetitive element is induced by herpesviruses
AU - Nogalski, Maciej T.
AU - Solovyov, Alexander
AU - Kulkarni, Anupriya S.
AU - Desai, Niyati
AU - Oberstein, Adam
AU - Levine, Arnold J.
AU - Ting, David T.
AU - Shenk, Thomas
AU - Greenbaum, Benjamin D.
N1 - Funding Information:
Competing interests: Icahn School of Medicine at Mt. Sinai and Princeton University have submitted a provisional patent application based on results reported in this manuscript, and M.T.N., A.S., T.S. and B.D.G. are inventors. The Institute for Advanced Study has a patent related to this work (WO 2016/131048 Al) on which B.D.G. and A.J.L. are inventors. B.D.G. has received honoraria for speaking engagements from Merck, Bristol–Meyers Squibb, and Chugai Pharmaceuticals, and has consulted for PMV Pharma. D.T.T. has performed consulting for Millipore-Sigma, Ventana-Roche, and Merrimack Pharmaceuticals and is a founder with equity in PanTher Therapeutics; none of these relationships are believed to be in conflict with this work. D.T.T. received consulting payments from Affymetrix, Inc. related to this work. D.T.T., A.S.K., and N.D. received sponsored research support from ACD-Biotechne and Affymetrix (formerly), which is related to this work. A.J.L. is a founder of PMV Pharmaceuticals, which synthesizes structural correctors for mutant p53 proteins. He has stock holdings in that company. A.J.L. is on the board of directors of Adaptive Biotechnologies (minimal residual diseases, diagnostics), Meira Corporation (ophthalmology, gene therapy), Genecentric Inc. (RNA seq, cancer classification and diagnosis), and has stock options in these companies. A.J.L. is the chair of the scientific advisory board of Janssen Pharmaceutical Company for which he has paid fees. A.J.L. is an advisor of WERB-Copernicus on the topic of IRB’s for which he receives a fee. T.S. is a founder of Forge Life Science (sirtuin modulators as anti-virals), ImmVira (oncolytic herpesviruses), and PMV Pharmaceuticals (structural correctors for mutant p53 proteins) and has stock holdings in those companies. T.S. is on the board of directors of MeiraGTx (ophthalmology, gene therapy) and Vical (anti-fungal agents), and receives fees, stock, and stock options from these companies. A.O. declares no competing interests.
Funding Information:
The authors would like to thank Dr. Alexander Ploss and Dr. Qiang Ding for providing the samples of ZIKV-and HCV-infected cells. The authors would also like to thank Drs. S. Jane Flint and Bernard Roizman for providing Ad5 and HSV-1 viruses, respectively. The authors thank Dr. Vikram Deshpande for assistance with colon samples and histologic interpretation. This work was supported by grants from the National Institutes of Health (AI112951 to T.S., 7R01AI081848-04 to B.D.G., and 1P30CA196521-01 to B.D.G. and A.S.). M.T.N. was supported by a fellowship from the American Cancer Society (PF-14-116-01 MPC). A.S. was supported by the V Foundation. B.D.G. and D.T.T. were supported by a Stand Up To Cancer–National Science Foundation–Lustgarten Foundation Convergence Dream Team Grant sponsored by Stand Up to Cancer, the Lust-garten Foundation, the V Foundation and the National Science Foundation (NSF 1545935). B.D.G. is The Pershing Square Sohn Prize—Mark Foundation Fellow supported by funding from The Mark Foundation for Cancer Research. D.T.T. was supported by the Burroughs Wellcome Fund. D.T.T., A.S.K., and N.D. were supported by Affymetrix, Inc. The results published here are in part based on data generated by the TCGA Research Network: http://cancergenome.nih.gov/.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-07944-x
DO - 10.1038/s41467-018-07944-x
M3 - Article
C2 - 30626867
AN - SCOPUS:85059795204
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 90
ER -