Related Experiment Videos
Differential distribution of sequence variations in HPV-16 E6.
B S Gostout1, G M Zanetta, S Maleemonkol
1Section of Gynecologic Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Gynecologic Oncology
|September 28, 2000
Summary
Human papillomavirus type 16 (HPV-16) E6 gene sequences from cervical cancers show significant variation, particularly in regions involved with p53 binding. This variation may impact immune recognition and viral function.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- The E6 gene of oncogenic human papillomaviruses (HPVs) plays a crucial role in cancer development and immune system evasion.
- HPV-16 is a high-risk HPV type frequently associated with cervical cancers.
Purpose of the Study:
- To investigate the frequency and extent of sequence variation in the HPV-16 E6 DNA from cervical cancer patients across different populations.
- To identify specific regions within the E6 gene that exhibit significant sequence diversity.
Main Methods:
- Analysis of HPV-16 E6 DNA sequences from cervical cancer samples using polymerase chain reaction (PCR) and automated DNA sequencing.
- Samples were collected from women in the U.S. (n=62), Italy (n=20), India (n=20), and Thailand (n=21).
Main Results:
- The HPV-16 E6 region is largely conserved, with 24 base substitutions found across 151 codons.
- HPV-16 E6 sequences from U.S. women exhibited greater variation compared to those from European and Asian women.
- The p53-binding and degradation domains showed notable sequence variation, while the carboxy-terminal end remained highly conserved.
Conclusions:
- The high-variation area includes a potential human leukocyte antigen (HLA) interaction site, suggesting implications for immune selection.
- A unique large deletion in one E6 sample led to the loss of all functional regions.
- Findings highlight the functional importance of the conserved carboxy end of the E6 protein and its potential role in immune evasion.