Cervical cancer-causing human papillomaviruses have an alternative initiation site for the L1 protein.
All known sequences of the DNA encoding the major cervical cancer-causing human papillomavirus type 16 (HPV16) L1 capsid protein contain initiation codons which would allow translation to begin at either nucleotide 5559 or 5637. However the formation of virus-like particles (VLPs) only occurs efficiently when the initiation codon at nucleotide 5637 is used for in vitro expression studies. This knowledge, in concert with the fact that virions have not been observed in HPV16-infected epithelium, raises the notion that the major L1 translation product in this HPV type may be largely confined to initiation at nucleotide 5559. Sequence analysis of various HPV types associated with particular clinical outcomes has revealed that L1 sequences of the major cervical cancer-associated viruses generally possess the ability to encode a longer translation product whilst the non-cancer-causing viruses do not. Equally intriguing, the upstream initiation codon is always separated by 78 nucleotides from the initiation codon that produces L1 protein which efficiently assembles into VLPs. We speculate that the longer L1 protein could play a role in the development of cervical carcinoma and that HPVs with the potential to cause cervical cancer may be identified by the presence of an in-frame ATG situated 78 nucleotides upstream.
Webb
Elizabeth
E
CSL Limited, 45 Poplar Road, Parkville, Victoria, Australia.
Cox
John
J
Edwards
Stirling
S
D001483:Base Sequence; D036022:Capsid Proteins; D018387:Codon, Initiator; D004279:DNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity; D014176:Protein Biosynthesis; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D022701:Virosomes / Q000096:biosynthesis
D036022:Capsid Proteins; D018387:Codon, Initiator; D004279:DNA, Viral; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D022701:Virosomes
J Gen Virol. 1995 May;76 ( Pt 5):1141-53
7537325
Virology. 1991 Nov;185(1):251-7
1656586
J Virol. 1986 Feb;57(2):688-92
3003400
J Gen Virol. 1989 Nov;70 ( Pt 11):3099-104
2555440
Hum Gene Ther. 2000 May 20;11(8):1165-76
10834618
N Engl J Med. 2003 Feb 6;348(6):518-27
12571259
Virology. 1991 Mar;181(1):203-10
1847256
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12180-4
1334560
Virology. 1991 Mar;181(1):419-23
1847266
Infect Immun. 1997 Aug;65(8):3328-36
9234794
J Virol. 1986 Jun;58(3):991-5
3009902
J Virol. 1991 Aug;65(8):4216-25
1649326
Virology. 1989 Jul;171(1):306-11
2545036
J Gen Virol. 1990 Sep;71 ( Pt 9):2185-90
2170578
J Gen Virol. 1988 Jun;69 ( Pt 6):1263-73
2838573
J Gen Virol. 1991 Dec;72 ( Pt 12):2981-8
1662690
Virology. 1985 Aug;145(1):181-5
2990099
J Virol. 1993 Dec;67(12):6929-36
8230414
Biochem Soc Trans. 1994 Aug;22(3):335S
7821591
Obstet Gynecol. 1992 Mar;79(3):328-37
1310805
N Engl J Med. 2002 Nov 21;347(21):1645-51
12444178
Virology. 1992 Feb;186(2):770-6
1310198
Virology. 1991 Jun;182(2):513-21
1850917
J Cell Biol. 1989 Feb;108(2):229-41
2645293