Molectilar Biology of Human Papillomaviruses 
malignancy. These observations also strongly 
support the etiological role of HPV in the devel- 
opment of cervical cancer. This work was sup- 
ported in part by a grant from the National Insti- 
tutes of Health. 
My laboratory has been able to identify factors 
involved in the cell type-specific regulation of 
viral gene expression and replication. We have 
-identified viral enhancer sequences that are re- 
sponsible for regulating viral expression in ma- 
turing keratinocytes. The function of one of these 
sequences is dependent on the action of a cellu- 
lar protein that is only found in epithelial cells. 
We have designated this protein keratinocyte- 
stimulating factor, KRF- 1 , and are currently clon- 
ing the gene that encodes it. 
Eventually we will examine how the action of 
cellular transcription factors is altered by the 
presence of viral transforming genes. We have 
shown that the products of both E6 and E7 can 
indirectly regulate the transcription of a variety 
of genes. In addition, we believe that a major de- 
terminant of the tissue spectrum of papillomavi- 
ruses is specified through the regulation of tran- 
scription. Understanding the mechanisms of 
tissue-specific expression will facilitate our anal- 
ysis of why different HPV types only induce le- 
sions in particular kinds of epithelial cells. Our 
studies on the biology of HPV should provide 
information on mechanisms of transformation 
and tumor progression, as well as tissue- and 
difi'erentiation-specific expression. 
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