Computer-assisted analysis of molecular mimicry between human papillomavirus 16 E7 oncoprotein and human protein sequences.
The immunology of human papillomavirus (HPV) infections has peculiar characteristics. The long latency for cervical cancer development after primary viral infection suggests mechanisms that may aid the virus in avoiding the host immunosurveillance and establishing persistent infections. In order to understand whether molecular mimicry phenomena might explain the ability of HPV to avoid a protective immune response by the host cell, sequence similarity between HPV16 E7 oncoprotein and human self-proteins was examined by computer-assisted analysis. Data were obtained showing that the HPV16 E7 protein has high and widespread similarity to several human proteins involved in a number of critical regulatory processes. In addition, multiple identical and different E7 peptide motifs are present in the same human protein. Thus, sharing of common motifs between viral oncoproteins and molecules of normal cells may be one cause underlying the scarce immunogenicity of HPV infections. The hypothesis is advanced that synthetic peptides harbouring viral motifs not and/or scarcely represented in the host's cellular proteins may represent a valuable immunotherapeutic approach for cervical cancer treatment.
Natale
C
C
General Surgery Division, United Hospitals, University of Foggia, Italy.
Giannini
T
T
Lucchese
A
A
Kanduc
D
D
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001330:Electronic Data Processing; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D000956:Antigens, Viral; D006680:HLA Antigens; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16