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Papillomaviruses induce benign epithelial proliferation (e.g., warts)
of the skin and mucosa. Individual papilloma-virus types are associated
with benign lesions whereas others are found in proliferative lesions
with a low or even considerable malignant potential.
Mucosal human papillomaviruses (HPV) cause cervical cancer and are
associated with a subset of head and neck cancers. In the infected cell,
productive papillomavirus particles are derived from extrachromosomal
viral plasmids. However, in many invasive HPV positive neoplasms, the
HPV DNA is partially deleted and integrated into the cell genomic DNA.
We have identiﬁed HPV-16 isolates that can establish persistent
replication and "immortalize" primary human foreskin, cervical and
tonsillar keratinocytes. Using primary keratinocytes and keratinocyte
derived cell lines we have developed assays that allow us study human
papilloma virus (HPV)-16 infection leading to persistence of replicating
viral plasmid genomes. Our system allows us to dissect the individual
viral factors required for this process. Studies are ongoing to
determine how the regulation of viral gene expression controls viral
Primary keratinocytes normally exhibit a limited life span in culture.
Introduction of HPV-16 into these cells extends their ability to divide
without limit. Many of the derived keratinocyte cultures exhibit no
detectable chromosomal alterations and contain 10-40 copies of
non-integrated plasmid HPV-16 DNA. Upon extended culture, cell lines may
spontaneously arise that overgrow the culture and contain only
integrated HPV-16 DNA and variable additional chromosomal abnormalities.
These cell lines have many similarities to cells of squamous carcinomas
that also contain integrated HPV. Studies are underway to determine the
role these genetic alterations play in altered cell growth and other
acquired phenotypes in these cell lines. These cell lines provide a
useful model system for the study of papillomavirus induced