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Journal of Virology, October 1998, p. 8115-8123, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Transactivation by the E2 Protein of Oncogenic
Human Papillomavirus Type 31 Is Not Essential for Early and Late
Viral Functions
Frank
Stubenrauch,
Angela
M. E.
Colbert, and
Laimonis
A.
Laimins*
Department of Microbiology-Immunology,
Northwestern University Medical School, Chicago, Illinois 60611
Received 2 April 1998/Accepted 13 July 1998
The activation of transcription and of DNA replication are, in some
cases, mediated by the same proteins. A prime example is the E2 protein
of human papillomaviruses (HPVs), which binds ACCN6GGT
sequences and activates heterologous promoters from multimerized binding sites. The E2 protein also has functions in replication, where it complexes with the virally encoded origin recognition protein,
E1. Much of the information on these activities is based on
transient-transfection assays as well as biochemical analyses; however,
their importance in the productive life cycle of oncogenic HPVs remains
unclear. To determine the contributions of these E2 functions to the
HPV life cycle, a genetic analysis was performed by using an
organotypic tissue culture model. HPV type 31 (HPV31) genomes that
contained mutations in the N terminus of E2 (amino acid 73) were
constructed; these mutants retained replication activities but were
transactivation defective. Following transfection of normal human
keratinocytes, these mutant genomes were established as stable episomes
and expressed early viral transcripts at levels similar to those of
wild-type HPV31. Upon differentiation in organotypic raft cultures, the
induction of late gene expression and amplification of viral DNA were
detected in cell lines harboring mutant genomes. Interestingly, only a
modest reduction in late gene expression was observed in the mutant
lines. We conclude that the transactivation function of E2 is not
essential for the viral life cycle of oncogenic HPVs, although it may
act to moderately augment late expression. Our studies suggest that the
primary positive role of E2 in the viral life cycle is as a replication
factor.
*
Corresponding author. Mailing address: Department of
Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Phone: (312) 503-0648. Fax: (312)
503-0649. E-mail: lal{at}merle.acns.nwu.edu.

Present address: Sektion Experimentelle Virologie,
Universitätsklinikum Tübingen, D-72076
Tübingen, Germany.
Journal of Virology, October 1998, p. 8115-8123, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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