Summary auto-generated
This study characterized genetic variation in human papillomavirus type 16 (HPV-16), a high-risk virus strongly associated with cervical cancer. Researchers analyzed nucleotide sequences of the E5 coding region and E2 hinge region in 48 clinical HPV-16 isolates from cervical cancer specimens and cervicovaginal samples using nested PCR and direct sequencing. The E5 region contained 14 nucleotide changes (6 synonymous, 8 nonsynonymous) producing 8 amino acid variations, while the E2 hinge region showed 18 nucleotide variations resulting in 13 nonsynonymous and 5 synonymous changes. Five amino acid variations were also observed in the overlapping E4 segment. The results identified sequence markers for major HPV-16 phylogenetic branches (European, Asian, Asian-American, and African variants) and a new sublineage within the Asian-American group. E5 substitutions were generally conservative, with strongest conservation in a transmembrane region critical for protein function. The authors suggest these sequence variants may alter viral biological functions and immune responses, and propose further studies to examine associations between specific HPV-16 variants and cervical cancer risk.
Key findings
- Eight amino acid variations identified in HPV-16 E5 coding segment and thirteen in E2 hinge region among 48 clinical isolates
- E5 substitutions highly conserved in putative transmembrane domain, indicating significant selective pressure despite overall poor conservation between HPV types
- E2 hinge region shows more nonsynonymous changes than E4 gene, suggesting less constraint on E2 amino acid conservation
- Nucleotide sequence markers identified for major HPV-16 phylogenetic branches and discovery of new Asian-American sublineage variant
- Sequence variations may affect viral transforming activity and immune responses, warranting functional studies and association analyses with cervical disease risk
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Abstract
We have previously examined 29 cervical cell isolates for human papillomavirus type 16 (HPV-16) sequence variations in the E6, L2 and L1 coding regions, and the long control region (LCR). Twenty-five of these isolates as well as 23 additional isolates are characterized here as we present the complete E5 coding segment and the E2 hinge region. Eight amino acid variations were observed in the E5 coding segment, 13 were identified in the E2 hinge region and 5 were observed in the overlapping E4 coding segment. These amino acid variations may be relevant to differences in biological functions and may result in altered humoral or cell-mediated immune responses to HPV-16 variants. The characterization of sequence variation within high-risk HPV types might be important in the search for epidemiological correlates of cervical cancer risk. This work complements and extends HPV-16 genome sequence information from specific isolates previously reported by our group.