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Human papillomavirus type 6: classification of clinical isolates and functional analysis of E2 proteins

Virology Program, Signal Pharmaceuticals Inc., 5555 Oberlin Drive, San Diego, CA 92121, USA¹
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA²
The Walther Cancer Institute, Indianapolis, IN 46202, USA³
Division of Infectious Diseases, Department of Medicine, Richard L. Roudebush VA Medical Center and Indiana University School of Medicine, Indianapolis, IN 46202, USA⁴

Author for correspondence: Robert Kovelman.Fax +1 619 623 0870. e-mail rkovelma{at}signalpharm.com

Human papillomaviruses (HPVs) cause a variety of clinical manifestations, including the most prevalent viral sexually transmitted disease, genital warts. HPV-6 is found in a greater number of genital warts than any other HPV. To increase our understanding of the structural and functional relationships between HPV-6 isolates and to provide information for epidemiological studies, the sequences of the E2, E6 and E7 coding regions of HPV-6 genomes in clinical samples were determined. This sequence analysis was performed on isolates originally designated HPV-6a on the basis of analysis of patterns generated by restriction enzyme digestion. It was found that the designation of subtype on the basis of restriction enzyme digestion correlated poorly with the designation of subtype on the basis of sequence comparison; in fact, the clinical isolates were clearly categorized into HPV-6a and HPV-6b groups, with the previously described HPV-6vc being a member of the HPV-6a group. It was also found that the HPV-6a E2 protein is a much less potent activator of transcription than the HPV-16 E2 protein, generalizing our previous results with the HPV-6b E2 protein to this second HPV-6 E2 protein. These studies indicate that the amino acid differences observed between these natural variants of the HPV-6 E2 protein do not affect its function.