title: Telomerase activity impacts on Epstein-Barr virus infection of AGS cells.
abstract: The Epstein-Barr virus (EBV) is transmitted from host-to-host via saliva and is associated with epithelial malignancies including nasopharyngeal carcinoma (NPC) and some forms of gastric carcinoma (GC). Nevertheless, EBV does not transform epithelial cells in vitro where it is rapidly lost from infected primary epithelial cells or epithelial tumor cells. Long-term infection by EBV, however, can be established in hTERT-immortalized nasopharyngeal epithelial cells. Here, we hypothesized that increased telomerase activity in epithelial cells enhances their susceptibility to infection by EBV. Using HONE-1, AGS and HEK293 cells we generated epithelial model cell lines with increased or suppressed telomerase activity by stable ectopic expression of hTERT or of a catalytically inactive, dominant negative hTERT mutant. Infection experiments with recombinant prototypic EBV (rB95.8), recombinant NPC EBV (rM81) with increased epithelial cell tropism compared to B95.8, or recombinant B95.8 EBV with BZLF1-knockout that is not able to undergo lytic replication, revealed that infection frequencies positively correlate with telomerase activity in AGS cells but also partly depend on the cellular background. AGS cells with increased telomerase activity showed increased expression mainly of latent EBV genes, suggesting that increased telomerase activity directly acts on the EBV infection of epithelial cells by facilitating latent EBV gene expression early upon virus inoculation. Thus, our results indicate that infection of epithelial cells by EBV is a very selective process involving, among others, telomerase activity and cellular background to allow for optimized host-to-host transmission via saliva.
authors: Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors: Jürgen
authors: J
authors: Rac
authors: Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors: Florian
authors: F
authors: Haas
authors: Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors: Andrina
authors: A
authors: Schumacher
authors: Department of Pathology and Cancer Center Amsterdam, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors: Jaap M
authors: JM
authors: Middeldorp
authors: Division of Pathogenesis of Virus Associated Tumors, German Cancer Research Center, Heidelberg, Germany.
authors: Henri-Jacques
authors: HJ
authors: Delecluse
authors: Division of Infectious Diseases and Hospital Epidemiology, Department of Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors: Roberto F
authors: RF
authors: Speck
authors: Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors: Michele
authors: M
authors: Bernasconi
authors: Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors: David
authors: D
authors: Nadal
mesh_terms: D002277:Carcinoma; D004261:DNA Replication / Q000235:genetics; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009305:Nasopharynx / Q000201:enzymology* / Q000473:pathology; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C509186:TERT protein, human; D019098:Telomerase