Perturbation of the host cell cycle and DNA replication by the bovine papillomavirus replication protein E1

被引:15
作者
Belyavskyi, M
Westerman, M
Dimichele, L
Wilson, VG
机构
[1] TEXAS A&M UNIV,COLL MED,DEPT MED MICROBIOL & IMMUNOL,COLLEGE STN,TX 77843
[2] TEXAS A&M UNIV,DEPT WILDLIFE & FISHERIES SCI,COLLEGE STN,TX 77843
关键词
D O I
10.1006/viro.1996.0238
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
A stable cell line expressing the bovine papillomavirus E1 protein (C2E1) was compared with an E1 minus control line (CNEO) to study the effects of E1 protein on host cell growth. C2E1 and CNEO cells were synchronized either at mitosis or at the G1/S boundary by the cell cycle inhibitors nocodazole and mimosine, respectively. After release from the drug-induced cell cycle block, the progression through the succeeding stages of the cell cycle was temporally monitored using flow cytometry. In addition, incorporation of bromodeoxyuridine (BrdUrd) was used to determine precisely the time of initiation of DNA synthesis in C2E1 and CNEO cells after release from drug-induced cell cycle arrest. Expression of E1 protein decreased the duration of G1 phase and increased S and G2 phase durations without affecting the overall cell doubling time. In conjunction with the increase in G2 phase duration, histone H1 kinase activity was prolonged during the G2 to M phase transition in C2E1 cells, which suggested that E1 protein may affect the mechanisms which ensure proper timing of kinase inactivation. During the G1 to S phase transition in C2E1 cells, the timing of appearance and abundance of cyclin D1 were altered compared to CNEO cells, while cyclin E levels were unaffected. Consequently, E1 protein may affect G1 phase duration through a cyclin D1-dependent pathway. Finally, a subpopulation of cells with a greater than G2 DNA content (>G2 DNA), and which was still capable of incorporating BrdUrd, was shown to exist only in the E1-expressing cell line. These combined results demonstrate that the viral replication protein E1 has the potential to influence the host cell environment significantly, which may contribute to pathogenesis and viral persistence. (C) 1996 Academic Press, Inc.
引用
收藏
页码:206 / 219
页数:14
相关论文
共 71 条
[61]   MAMMALIAN G(1)-CYCLINS [J].
SHERR, CJ .
CELL, 1993, 73 (06) :1059-1065
[62]  
SLADEK TL, 1992, J VIROL, V68, P1059
[63]   Activation of the various cyclin/cdc2 protein kinases [J].
Solomon, Mark J. .
CURRENT OPINION IN CELL BIOLOGY, 1993, 5 (02) :180-186
[64]   THE STRUCTURE, FUNCTION, AND REGULATION OF PAPILLOMAVIRAL GENES IN INFECTION AND CERVICAL-CANCER [J].
TUREK, LP .
ADVANCES IN VIRUS RESEARCH, VOL 44, 1994, 44 :305-356
[65]   IDENTIFICATION OF THE ORIGIN OF REPLICATION OF BOVINE PAPILLOMAVIRUS AND CHARACTERIZATION OF THE VIRAL ORIGIN RECOGNITION FACTOR-E1 [J].
USTAV, M ;
USTAV, E ;
SZYMANSKI, P ;
STENLUND, A .
EMBO JOURNAL, 1991, 10 (13) :4321-4329
[66]   TRANSIENT REPLICATION OF BPV-1 REQUIRES 2 VIRAL POLYPEPTIDES ENCODED BY THE E1 AND E2 OPEN READING FRAMES [J].
USTAV, M ;
STENLUND, A .
EMBO JOURNAL, 1991, 10 (02) :449-457
[67]   INTERACTIONS BETWEEN PAPILLOMAVIRUS PROTEINS AND TUMOR-SUPPRESSOR GENE-PRODUCTS [J].
VOUSDEN, KH .
ADVANCES IN CANCER RESEARCH, VOL 64, 1994, 64 :1-24
[68]   MIMOSINE REVERSIBLY ARRESTS CELL-CYCLE PROGRESSION AT THE G1-S PHASE BORDER [J].
WATSON, PA ;
HANAUSKEABEL, HH ;
FLINT, A ;
LALANDE, M .
CYTOMETRY, 1991, 12 (03) :242-246
[69]   THE RETINOBLASTOMA PROTEIN AND CELL-CYCLE CONTROL [J].
WEINBERG, RA .
CELL, 1995, 81 (03) :323-330
[70]   ROLE OF TRANSCRIPTIONAL REPRESSORS IN TRANSFORMATION BY BOVINE PAPILLOMAVIRUS TYPE-1 [J].
ZEMLO, TR ;
LOHRBACH, B ;
LAMBERT, PF .
JOURNAL OF VIROLOGY, 1994, 68 (10) :6787-6793