Comparative analysis of 19 genital human papillomavirus types with regard to p53 degradation, immortalization, phylogeny, and epidermiologic risk classification

被引:68
作者
Hiller, Thomas [1 ]
Poppelreuther, Sven [1 ]
Stubenrauch, Frank [1 ]
Iftner, Thomas [1 ]
机构
[1] Univ Klinikum Tuebingen, Sekt Expt Virol, D-72076 Tubingen, Germany
关键词
D O I
10.1158/1055-9965.EPI-05-0778
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have analyzed E6 proteins of 19 papillomaviruses able to infect genital tissue with regard to their ability to degrade p53 and the thus far unknown immortalization potential of the genomes of human papillomaviruses (HPV) 53, 56, 58, 61, 66, and 82 in primary human keratinocytes. E6 proteins of HPV types 16, 18, 33, 35, 39, 45, 51, 52, 56, 58, and 66, defined as high-risk types, were able to induce p53 degradation in vitro, and HPV18-, HPV56-, and HPV58-immortalized keratinocytes revealed markedly reduced levels of p53. In contrast, the E6 proteins of HPV6 and 11 and HPV44, 54, and 61, regarded as possible carcinogenic or low-risk HPV types, respectively, did not degrade p53. Interestingly, the E6 proteins of HPV 53, 70, and 82 inconsistently risk classified in the literature were also found to induce p53 degradation. The genomes of HPV53 and 82 immortalized primary human keratinocytes that revealed almost absent nuclear levels of p53. These data suggest a strict correlation between the biological properties of certain HPV types with conserved nucleotide sequence (phylogeny), which is largely coherent with epidemiologic risk classification. HPV types 16, 18, 33, 35, 39, 45, 51, 52, 56, 58, and 66, generally accepted as high-risk types, behaved in our assays biologically different from HPV types 6, 11, 44, 54, and 61. In contrast, HPV70, regarded as low-risk type, and HPV53 or HPV82, with inconsistent described risk status, were indistinguishable with respect to p53 degradation and immortalization from prototype high-risk HPV types. This could imply that other important functional differences exist between phylogenetically highly related viruses displaying similar biological properties in tissue culture that may affect their carcinogenicity in vivo.
引用
收藏
页码:1262 / 1267
页数:6
相关论文
共 38 条
[1]  
BARBOSA MS, 1989, ONCOGENE, V4, P1529
[2]   The causal relation between human papillomavirus and cervical cancer [J].
Bosch, FX ;
Lorincz, A ;
Muñoz, N ;
Meijer, CJLM ;
Shah, KV .
JOURNAL OF CLINICAL PATHOLOGY, 2002, 55 (04) :244-265
[3]   Mucosal human papillomaviruses encode four different E5 proteins whose chemistry and phylogeny correlate with malignant or benign growth [J].
Bravo, IG ;
Alonso, A .
JOURNAL OF VIROLOGY, 2004, 78 (24) :13613-13626
[4]   Induction of apoptosis in human papillomavirus-positive cancer cells by peptide aptamers targeting the viral E6 oncoprotein [J].
Butz, K ;
Denk, C ;
Ullmann, A ;
Scheffner, M ;
Hoppe-Seyler, F .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) :6693-6697
[5]   Carcinogenicity of human papillomaviruses [J].
Cogliano, V ;
Baan, R ;
Straif, K ;
Grosse, Y ;
Secretan, B ;
El Ghissassi, F .
LANCET ONCOLOGY, 2005, 6 (04) :204-204
[6]   Classification of papillomaviruses [J].
de Villiers, EM ;
Fauquet, C ;
Broker, TR ;
Bernard, HU ;
zur Hausen, H .
VIROLOGY, 2004, 324 (01) :17-27
[7]  
Delius H, 1994, Curr Top Microbiol Immunol, V186, P13
[8]  
DURST M, 1987, ONCOGENE, V1, P251
[9]   Human papillomavirus type 70 genome cloned from overlapping PCR products: Complete nucleotide sequence and genomic organization [J].
Forslund, O ;
Hansson, BG .
JOURNAL OF CLINICAL MICROBIOLOGY, 1996, 34 (04) :802-809
[10]   In vitro synthesis of oncogenic human papillomaviruses requires episomal genomes for differentiation-dependent late expression [J].
Frattini, MG ;
Lim, HB ;
Laimins, LA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) :3062-3067