title: Human papillomavirus 16E6 suppresses major histocompatibility complex class I by upregulating lymphotoxin expression in human cervical cancer cells.
abstract: Major histocompatibility complex (MHC) class I is a major host defense mechanism against viral infections such as type 16 and type 18 of the human papillomavirus (HPV). Here, we found that the E6 oncogene from HPV16, but not HPV18, suppressed MHC I expression. Ectopic expression of HPV16E6 in HeLa cells, which are infected with HPV18, suppressed MHC I expression, and that knockdown by antisense or siRNA of the HPV16E6 strongly enhanced MHC I expression in Caski cells, which are infected with HPV18, but not HPV16. The expression of HPV16E6 strongly enhanced cellular resistance to cytotoxic T lymphocytes (CTLs)-mediated lytic activity, and knockdown of HPV16E6 by antisense had the opposite effect. The regulation of HPV16E6-mediated MHC I suppression might be through the regulation of lymphotoxin (LT) and its receptor, LTβR. In addition, cells from the spleen and liver of LTα- or LTβR-deficient mice showed increased MHC I expression. Overall, these results demonstrated that the E6 oncogene of HPV16 might play an important role in cell transformation and cancer development through LT-mediated MHC I downregulation in humans.
authors.affiliation: School of Biological Sciences and Technology, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Republic of Korea.
authors.forename: Dong-Hern
authors.initials: DH
authors.lastname: Kim
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Kim
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Lee
authors.forename: Kon-Young
authors.initials: KY
authors.lastname: Ji
authors.forename: Jawoon
authors.initials: J
authors.lastname: Yi
authors.forename: Min
authors.initials: M
authors.lastname: Park
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
authors.forename: Yong-Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Kang
mesh_terms: D000818:Animals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D052162:Human papillomavirus 16 / Q000235:genetics*; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D053259:Lymphotoxin beta Receptor / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics*; D053308:Lymphotoxin-beta / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D015395:Histocompatibility Antigens Class I; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins