HPV16 E2 protein promotes innate immunity by modulating immunosuppressive status

Nuchsupha Sunthamala; Chamsai Pientong; Tatsukuni Ohno; Chenyang Zhang; Arundhati Bhingare; Yuta Kondo; Miyuki Azuma; Tipaya Ekalaksananan

doi:10.1016/j.bbrc.2014.03.042

HPV16 E2 protein promotes innate immunity by modulating immunosuppressive status

Biochem Biophys Res Commun. 2014 Apr 18;446(4):977-82. doi: 10.1016/j.bbrc.2014.03.042. Epub 2014 Mar 18.

Authors

Nuchsupha Sunthamala¹, Chamsai Pientong², Tatsukuni Ohno³, Chenyang Zhang³, Arundhati Bhingare³, Yuta Kondo³, Miyuki Azuma⁴, Tipaya Ekalaksananan⁵

Affiliations

¹ Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
² Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
³ Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
⁴ Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. Electronic address: miyuki.mim@tmd.ac.jp.
⁵ Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: tipeka@kku.ac.th.

PMID: 24657154
DOI: 10.1016/j.bbrc.2014.03.042

Abstract

The balance between active immune responses against human papillomavirus (HPV) and HPV-induced immune escape regulates viral clearance and carcinogenesis. To understand the role of the early viral protein HPV16 E2 in host innate immune responses, the HPV16 E2-transfected murine squamous cell carcinoma cell line SCCVII (SCC/E2) was generated and anti-tumor responses in T-cell-depleted mice were evaluated. Tumor growth of SCC/E2 was markedly reduced. Cytotoxicity against the NK-sensitive targets YAC-1 and SCCVII was clearly enhanced in SCC/E2-inoculated mice. Despite the comparable ratio of NK cells, the proportion of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) was significantly decreased in SCC/E2-inoculated mice. The transcription of MDSC-related mediators such as inducible nitric oxide synthase, indoleamine 2,3-dioxygenase, and heme oxygenase-1 was significantly impaired in the SCC/E2-inoculated tumor tissues on day 3. Our results suggest that HPV16 E2 promotes anti-tumor innate effector function by modulating immunoregulatory events mediated by MDSCs and their mediators. This report describes a new role for HPV16 E2 as a local immunomodulator at infected sites.

Keywords: Human papillomavirus; Immunosuppression; Myeloid-derived suppressor cells; NK cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Squamous Cell / immunology*
Carcinoma, Squamous Cell / pathology
Carcinoma, Squamous Cell / virology*
Cell Line, Tumor
Chemokines / immunology
DNA-Binding Proteins / genetics
DNA-Binding Proteins / immunology*
Female
Heme Oxygenase-1 / immunology
Host-Pathogen Interactions*
Human papillomavirus 16 / physiology*
Humans
Immunity, Innate*
Killer Cells, Natural / immunology
Killer Cells, Natural / virology*
Mice
Oncogene Proteins, Viral / genetics
Oncogene Proteins, Viral / immunology*
Transfection

Substances

Chemokines
DNA-Binding Proteins
E2 protein, Human papillomavirus type 16
Oncogene Proteins, Viral
Heme Oxygenase-1