Low risk HPV‑6E6 induces apoptosis in bone marrow‑derived dendritic cells

Sun,Lina; Zhao,Lei; Li,Dan; Xu,Shuai; Hou,Xuexin; Li,Zhenjun

doi:10.3892/ol.2017.7417

Low risk HPV‑6E6 induces apoptosis in bone marrow‑derived dendritic cells

Authors:
- Lina Sun
- Lei Zhao
- Dan Li
- Shuai Xu
- Xuexin Hou
- Zhenjun Li
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Affiliations: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China, Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa, IA 52242, USA
Published online on: November 15, 2017 https://doi.org/10.3892/ol.2017.7417
Pages: 1157-1162

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Abstract

The present study assessed the subcellular localization and apoptotic potential of low‑risk human papilloma virus 6E6 (HPV‑6E6), expressed in bone marrow‑derived dendritic cells (DCs). DCs were obtained from C57BL/6 mice and transfected with a pGFP‑6E6 plasmid. The subcellular localization of E6 was determined by tracing green fluorescent protein (GFP) using fluorescence microscopy. Apoptosis was assessed by staining nuclei with DAPI and performing an apoptosis‑based flow cytometry assay. The co‑localization of E6 and p53 was also investigated using confocal microscopy. In addition, the expression of apoptosis‑associated proteins was analyzed using immunoblotting. The results of the present study demonstrated that low‑risk HPV‑6E6 is predominantly localized in the cytoplasm of DCs. Furthermore, p53 was upregulated in DCs transfected with pGFP‑6E6 and co‑localized with GFP‑6E6 in the cytoplasm. DCs transfected with a control pGFP plasmid did not undergo apoptosis, whereas cells transfected with pGFP‑6E6 did, as indicated by the presence of cell debris and condensation of the nuclei. Furthermore, the expression of apoptosis‑associated proteins, including p53, BCL2 associated X apoptosis regulator (Bax), BCL2 homologous antagonist/killer (Bak) and cytochrome c, were significantly higher in DCs expressing low‑risk E6 than in control cells. Therefore, the current study demonstrated that low‑risk HPV‑6E6 is predominantly located in the cytoplasm of DCs and induces apoptosis. This may be an important mechanism that explains why low‑risk HPV is unable to induce malignant transformation.

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