title: Human papillomavirus promotes Epstein-Barr virus maintenance and lytic reactivation in immortalized oral keratinocytes.
abstract: Epstein-Barr virus and human papillomaviruses are human tumor viruses that infect and replicate in upper aerodigestive tract epithelia and cause head and neck cancers. The productive phases of both viruses are tied to stratified epithelia highlighting the possibility that these viruses may affect each other's life cycles. Our lab has established an in vitro model system to test the effects of EBV and HPV co-infection in stratified squamous oral epithelial cells. Our results indicate that HPV increases maintenance of the EBV genome in the co-infected cells and promotes lytic reactivation of EBV in upper layers of stratified epithelium. Expression of the HPV oncogenes E6 and E7 were found to be necessary and sufficient to account for HPV-mediated lytic reactivation of EBV. Our findings indicate that HPV increases the capacity of epithelial cells to support the EBV life cycle, which could in turn increase EBV-mediated pathogenesis in the oral cavity.
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, United States.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Makielski
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, United States.
authors.forename: Denis
authors.initials: D
authors.lastname: Lee
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, United States.
authors.forename: Laurel D
authors.initials: LD
authors.lastname: Lorenz
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, United States.
authors.forename: Dhananjay M
authors.initials: DM
authors.lastname: Nawandar
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, United States; Morgridge Institute for Research, University of Wisconsin-Madison, 330 N. Orchard Street, Madison, WI 53715, United States.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Chiu
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, United States.
authors.forename: Shannon C
authors.initials: SC
authors.lastname: Kenney
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, United States. Electronic address: plambert@wisc.edu.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lambert
mesh_terms: D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000821:virology*; D009061:Mouth Mucosa / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae / Q000145:classification / Q000502:physiology*; D013559:Symbiosis; D046509:Tissue Culture Techniques; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D009856:Oncogene Proteins, Viral
keywords: E6; E7; EBV; HPV; Latency; Life-Cycle; Lytic; Organotypic culture