Quantitative Role of the Human Papillomavirus Type 16 E5 Gene during the Productive Stage of the Viral Life Cycle

Genther, Sybil M.; Sterling, Stephanie; Duensing, Stefan; Münger, Karl; Sattler, Carol A.; Lambert, Paul F.

doi:10.1128/jvi.77.5.2832-2842.2003

Cited by 151 publications

(153 citation statements)

References 48 publications

(44 reference statements)

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“…The E5 stimulates the transforming activity of the epidermal growth factor receptor resulting in increased cell proliferaction (Pim et al 1992). In a raft culture model, the E5 was shown to support cellular DNA synthesis in suprabasal cells and neither viral late gene expression nor epithelial differentiation was affected by the E5 (Genther et al 2003). The E5 protects human foreskin keratinocytes from ultraviolet B-irradiation-induced apoptosis .…”

Section: E5 Proteinmentioning

confidence: 97%

Human papillomavirus type 16 in head and neck carcinogenesis

2005

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Section: E5 Proteinmentioning

confidence: 97%

Human papillomavirus type 16 in head and neck carcinogenesis

2005

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“…It has also been shown that E5 alters the growth and differentiation of stratified epithelia and induces epithelial tumors at a high frequency in mice (Genther Williams et al, 2005). Moreover, important functions in late stages of viral replication have been suggested (Fehrmann et al, 2003;Genther et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Genes involved in cell adhesion, cell motility and mitogenic signaling are altered due to HPV 16 E5 protein expression

et al. 2007

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We investigated the effects of the human papillomavirus type 16 E5 oncogene on cellular gene expression in human epithelial cells using cDNA microarray. In a genome-wide microarray assay, the expression of 179 genes was found to be significantly altered due to E5 expression. The expression of lamin A/C was downregulated at protein level. The expression of protein kinase C-d and phosphoinositide-3-kinase proteins was found to be upregulated. We also observed increased motility of E5-expressing cells. We conclude that the E5 protein affects several cellular pathways involved in cell adhesion, cell motility and mitogenic signaling. These alterations may together lead to inhibition of apoptosis and facilitate the establishment of persistent infection in the epithelium.

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“…HPV perturbs multiple aspects of this differentiation program including the withdrawal of cells from the cell cycle and the expression of differentiation-specific cellular genes. Most notably, suprabasal cells that harbor HPV genomes undergo DNA synthesis and have delayed expression of differentiation-specific proteins (11,12,16,24). These changes induced by the virus are thought to be critical for the synthesis of viral genomic DNA and its encapsidation to form progeny virus (24).…”

mentioning

confidence: 99%

Interactions with Pocket Proteins Contribute to the Role of Human Papillomavirus Type 16 E7 in the Papillomavirus Life Cycle

Collins

Nakahara

et al. 2005

J Virol

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Human papillomaviruses (HPVs), most commonly the HPV16 genotype, are the principle etiological determinant for cervical cancer, a common cancer worldwide resulting in over 200,000 deaths annually. The oncogenic properties of HPVs are attributable in part to the virally encoded protein E7, best known for its ability to bind to and induce the degradation of the retinoblastoma tumor suppressor, pRb, and related "pocket proteins" p107 and p130. Previously, we defined a role for E7 in the productive stage of the HPV16 life cycle, which takes place in stratified squamous epithelia. HPV perturbs the normal processes of cell growth and differentiation of stratified squamous epithelia. HPVs reprogram cells to support continued DNA synthesis and inhibit their differentiation in the suprabasal compartment of the epithelia, where cells normally have withdrawn from the cell cycle and initiated a well-defined pattern of terminal differentiation. These virus-induced perturbations, which contribute to the production of progeny HPVs, are dependent on E7. In this study, we define the mechanism of action by which E7 contributes to the productive stage of the HPV16 life cycle. We found that the ability of HPV16 to reprogram suprabasal cells to support DNA synthesis correlates with E7's ability to bind pocket proteins but not its ability to induce their degradation. In contrast, the ability of HPV16 to perturb differentiation correlated with both E7's binding to and degradation of pocket proteins. These data indicate that different hallmarks of the productive stage of the HPV16 life cycle rely upon different sets of requirements for E7.Human papillomaviruses (HPVs) are small DNA tumor viruses that infect stratified squamous epithelial cells. There are over 100 genotypes of HPV that are classified as cutaneous or mucosotropic, based on whether they primarily infect the skin or the anogenital tract/cavity, respectively. The mucosotropic HPVs are further subclassified as low or high risk, depending on their etiological association with human cancers. High-risk HPVs, such as HPV16, are accepted as the main causal factor for cervical cancer, a leading cause of death among women worldwide, and other less common anogenital cancers including cancers of the vagina, vulva, penis, and anus (50, 52). In addition, high-risk HPVs are associated with a subset of oral cancers (17, 52). One of the HPV genes implicated in HPVassociated cancer is E7 (23,26,34,44). E7 also plays a critical role in the viral life cycle by reprogramming cells within the suprabasal compartment of stratified squamous epithelia to support DNA synthesis, a prerequisite for viral DNA amplification and production of progeny virus (12). E7 is a multifunctional protein best known for its ability to bind and inactivate the retinoblastoma tumor suppressor, pRb, and related "pocket proteins" p107 and p130 (10,28,36,42). In this study, we examined the mechanism of action by which E7 contributes to the viral life cycle and, in particular, the importance of E7 interaction with pRb and...

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Quantitative Role of the Human Papillomavirus Type 16 E5 Gene during the Productive Stage of the Viral Life Cycle

Cited by 151 publications

References 48 publications

Human papillomavirus type 16 in head and neck carcinogenesis

Human papillomavirus type 16 in head and neck carcinogenesis

Genes involved in cell adhesion, cell motility and mitogenic signaling are altered due to HPV 16 E5 protein expression

Interactions with Pocket Proteins Contribute to the Role of Human Papillomavirus Type 16 E7 in the Papillomavirus Life Cycle

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