# HUMAN PAPILLOMAVIRUS GENE EXPRESSION

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 1993 · $472,042

## Abstract

Human papillomaviruses (HPVs) are widespread and important pathogens that
cause both benign and malignant epithelial lesions, most notably various
types of cutaneous warts, genital warts, laryngeal papillomas, and
cervical and penile dysplasias and carcinomas.  Infections by the
mucosotrophic HPVs are the most prevalent sexually transmitted diseases
of viral etiology.  Papillomaviruses have stringent species and tissue
tropisms and cannot be propagated in conventional cell cultures.
Recently we and others have succeeded in replicating HPV DNA in
transiently transfected cells and also in recapitulating the viral
productive program by culturing tissues or cells that harbor episomal HPV
DNAs at the medium-air interface on a dermal equivalent of collagen
containing fibroblasts (i.e., as raft cultures).  Tremendous strides have
also been made in many laboratories in understanding other aspects of the
molecular and cellular biology of the viruses and their host cells on the
basis of studies performed with cloned genes and regulatory sequences and
with patient biopsies.  However, there are still significant unanswered
questions concerning viral DNA replication, mRNA transcriptional
regulation, viral protein functions, virus-host interactions and
pathogenesis.  The overall goal of this application is to perform a
genetic dissection the papillomavirus in the context of its productive
program in differentiating epithelium.  The roles of viral cis sequence
elements and trans-acting E1 and E2 proteins in extra-chromosomal DNA
replication will be further investigated in a cell-free system and in
transiently transfected cells.  The functions of the other E region
proteins and the regulatory sequences will be studied in primary human
keratinocytes (PHK) cultured by the collagen raft technique.  To achieve
these goals, efficient means for introducing wild type or mutant viral
DNAs into PHK will be developed, including packaging DNA into virions in
surrogate cells.  The mechanisms by which viral proteins activate host
genes essential for DNA replication, a necessity for viral propagation
in differentiated cells that have long exited from the cell cycle, will
continue to be examined.  Finally, the epithelial raft culture system
provides an opportunity to design and test specific antiviral therapeutic
agents.  We will explore the possibilities of using sequence-specific
triplex-forming oligonucleotides targeted to the regulatory region to
interfere with viral transcription and replication.

## Key facts

- **NIH application ID:** 3173710
- **Project number:** 2R01CA036200-09
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **SAM.gov UEI:** YND4PLMC9AN7
- **Principal Investigator:** LOUISE T CHOW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $472,042
- **Award type:** 2
- **Project period:** 1984-08-01 → 1997-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173710

## Citation

> US National Institutes of Health, RePORTER application 3173710, HUMAN PAPILLOMAVIRUS GENE EXPRESSION (2R01CA036200-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173710. Licensed CC0.

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