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 charac teristics. The long latency for cervical cancer development after primary v iral infection suggests mechanisms that may aid the virus in avoiding the h ost 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 simil arity between HPV16 E7 oncoprotein and human self-proteins was examined by computer-assisted analysis. Data were obtained showing that the HPV16 E7 pr otein has high and widespread similarity to several human proteins involved in a number of critical regulatory processes. In addition, multiple identi cal 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 i nfections. The hypothesis is advanced that synthetic peptides harbouring vi ral motifs not and/or scarcely represented in the host's cellular proteins may represent a valuable immunotherapeutic approach for cervical cancer tre atment.