The full-length E1-circumflexE4 protein of human papillomavirus type 18 modulates differentiation-dependent viral DNA amplification and late gene expression

Journal Article · Tue Jun 05 04:00:00 EDT 2007 · Virology

DOI:https://doi.org/10.1016/j.virol.2007.01.005· OSTI ID:20977032

Wilson, Regina ^[1]; Ryan, Gordon B ^[2]; Knight, Gillian L ^[2]; Laimins, Laimonis A ^[1]; Roberts, Sally ^[2]

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1. Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (United States)
2. Cancer Research UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT (United Kingdom)

Activation of the productive phase of the human papillomavirus (HPV) life cycle in differentiated keratinocytes is coincident with high-level expression of E1-circumflexE4 protein. To determine the role of E1-circumflexE4 in the HPV replication cycle, we constructed HPV18 mutant genomes in which expression of the full-length E1-circumflexE4 protein was abrogated. Undifferentiated keratinocytes containing mutant genomes showed enhanced proliferation when compared to cells containing wildtype genomes, but there were no differences in maintenance of viral episomes. Following differentiation, cells with mutant genomes exhibited reduced levels of viral DNA amplification and late gene expression, compared to wildtype genome-containing cells. This indicates that HPV18 E1-circumflexE4 plays an important role in regulating HPV late functions, and it may also function in the early phase of the replication cycle. Our finding that full-length HPV18 E1-circumflexE4 protein plays a significant role in promoting viral genome amplification concurs with a similar report with HPV31, but is in contrast to an HPV11 study where viral DNA amplification was not dependent on full-length E1-circumflexE4 expression, and to HPV16 where only C-terminal truncations in E1-circumflexE4 abrogated vegetative genome replication. This suggests that type-specific differences exist between various E1-circumflexE4 proteins.

• OSTI ID: 20977032
• Journal Information: Virology, Journal Name: Virology Journal Issue: 2 Vol. 362; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMPLIFICATION
CELL PROLIFERATION
DNA
GENES
HUMAN POPULATIONS
LIFE CYCLE
MUTANTS
PROTEINS