Differential distribution of sequence variations in HPV-16 E6.
OBJECTIVE
The E6 regions of the oncogenic human papillomaviruses (HPVs) are important in carcinogenesis and immune recognition. We examined the E6 DNA sequence from HPV-16-associated cervical cancers to determine the frequency and degree of variation from the consensus sequence in selected populations.


METHODS
Samples positive for HPV-16 were analyzed using polymerase chain reaction followed by automated DNA sequencing: 62 from U.S. women, 20 each from Italian and Indian women, and 21 from Thai women.


RESULTS
Of 151 codons, 18 contained 24 base substitutions, reflecting the overall conserved nature of this region. The HPV-16 E6 region from U. S. women showed considerably more sequence variation than that from European and Asian women. Five patterns common to U.S. and European and Asian samples accounted for 78% of all tumor-associated viruses. The E6 regions known to be involved in p53 binding and degradation are involved with a surprising degree of sequence variation, whereas the carboxy end of the molecule is highly conserved.


CONCLUSIONS
The area of greatest sequence variation includes a proposed human leukocyte antigen interaction site. A novel large deletion in one sample results in loss of all functional regions of E6. These findings were analyzed for possible significance with regard to immune selection and functional importance of the carboxy end of the E6 protein.
Gostout
B S
BS
Section of Gynecologic Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Zanetta
G M
GM
Maleemonkol
S
S
Kamat
M R
MR
McGovern
R M
RM
Persing
D H
DH
D000595:Amino Acid Sequence; D016384:Consensus Sequence; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D010449:Peptide Mapping; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D002578:Uterine Cervical Dysplasia / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000821:virology*
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins