HPV6 variants from malignant tumors with sequence alterations in the regulatory region do not reveal differences in the activities of the oncogene promoters but do contain amino acid exchanges in the E6 and E7 proteins

被引:32
作者
Grassmann, K
Wilczynski, SP
Cook, N
Rapp, B
Iftner, T
机构
[1] INST KLIN & MOL VIROL, D-91054 ERLANGEN, GERMANY
[2] CITY HOPE NATL MED CTR, DEPT ANAT PATHOL, DUARTE, CA 91010 USA
关键词
D O I
10.1006/viro.1996.0467
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human papillomavirus type 6 (HPV6) causes benign epithelial proliferations of the anogenital and aerodigestive tract, which usually tend to regress spontaneously. The low incidence of HPV6 in carcinomas and the rare progression of the benign tumors has led to the classification of HPV6 as ''low-risk'' virus. A series of reports, however, described the isolation of HPV6 variants from malignant tumors characterized by sequence rearrangements in the noncoding regulatory region (NCR). It was speculated that these sequence alterations play a role in tumor progression by enhancing the promoter activity and thereby increasing the expression of the viral oncogenes E6 and E7. To elucidate if HPV6 isolates from malignancies do regularly exhibit sequence alterations in the regulatory region we first determined and compiled the sequences of the NCRs of a number of isolates from benign and malignant lesions. This analysis revealed in general a high degree of sequence conservation between the individual isolates. Most of the isolates, however, differed, independently of origin, by a major and one or two minor insertions from the prototype HPV6b sequence. When tested in a functional assay these altered NCR sequences did not result in significantly different activities of the promoters responsible for the expression of the E6 and E7 genes. Further analysis of the E6 and E7 coding region revealed a surprisingly high sequence variability within the E6 ORF and allowed the detection of amino acid exchanges unique for isolates from carcinomas. (C) 1996 Academic Press, Inc.
引用
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页码:185 / 197
页数:13
相关论文
共 73 条
[21]   PARTIAL CHARACTERIZATION OF VIRAL-DNA FROM HUMAN GENITAL WARTS (CONDYLOMATA-ACUMINATA) [J].
GISSMANN, L ;
HAUSEN, HZ .
INTERNATIONAL JOURNAL OF CANCER, 1980, 25 (05) :605-609
[22]   HUMAN PAPILLOMAVIRUS TYPE-6 AND TYPE-11 DNA-SEQUENCES IN GENITAL AND LARYNGEAL PAPILLOMAS AND IN SOME CERVICAL CANCERS [J].
GISSMANN, L ;
WOLNIK, L ;
IKENBERG, H ;
KOLDOVSKY, U ;
SCHNURCH, HG ;
ZURHAUSEN, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (02) :560-563
[23]  
GISSMANN L, 1982, INT J CANCER, V29, P143, DOI 10.1002/ijc.2910290205
[24]   THE UPSTREAM REGULATORY REGION OF THE HUMAN PAPILLOMA VIRUS-16 CONTAINS AN E2-PROTEIN-INDEPENDENT ENHANCER WHICH IS SPECIFIC FOR CERVICAL-CARCINOMA CELLS AND REGULATED BY GLUCOCORTICOID HORMONES [J].
GLOSS, B ;
BERNARD, HU ;
SEEDORF, K ;
KLOCK, G .
EMBO JOURNAL, 1987, 6 (12) :3735-3743
[25]   NEW TECHNIQUE FOR ASSAY OF INFECTIVITY OF HUMAN ADENOVIRUS 5 DNA [J].
GRAHAM, FL ;
VANDEREB, AJ .
VIROLOGY, 1973, 52 (02) :456-467
[26]   Identification of a differentiation-inducible promoter in the E7 open reading frame of human papillomavirus type 16 (HPV-16) in raft cultures of a new cell line containing high copy numbers of episomal HPV-16 DNA [J].
Grassmann, K ;
Rapp, B ;
Maschek, H ;
Petry, KU ;
Iftner, T .
JOURNAL OF VIROLOGY, 1996, 70 (04) :2339-2349
[27]   HUMAN PAPILLOMAVIRUSES IN THE PATHOGENESIS OF ANOGENITAL CANCER [J].
HAUSEN, HZ .
VIROLOGY, 1991, 184 (01) :9-13
[28]   EFFICIENCY OF BINDING THE RETINOBLASTOMA PROTEIN CORRELATES WITH THE TRANSFORMING CAPACITY OF THE E7 ONCOPROTEINS OF THE HUMAN PAPILLOMAVIRUSES [J].
HECK, DV ;
YEE, CL ;
HOWLEY, PM ;
MUNGER, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) :4442-4446
[29]   FUNCTIONAL MAPPING OF THE HUMAN PAPILLOMAVIRUS TYPE-11 TRANSCRIPTIONAL ENHANCER AND ITS INTERACTION WITH THE TRANS-ACTING E2 PROTEINS [J].
HIROCHIKA, H ;
HIROCHIKA, R ;
BROKER, TR ;
CHOW, LT .
GENES & DEVELOPMENT, 1988, 2 (01) :54-67
[30]   SEQUENCE DETERMINATION OF HUMAN PAPILLOMAVIRUS TYPE 6A AND ASSEMBLY OF VIRUS-LIKE PARTICLES IN SACCHAROMYCES-CEREVISIAE [J].
HOFMANN, KJ ;
COOK, JC ;
JOYCE, JG ;
BROWN, DR ;
SCHULTZ, LD ;
GEORGE, HA ;
ROSOLOWSKY, M ;
FIFE, KH ;
JANSEN, KU .
VIROLOGY, 1995, 209 (02) :506-518