Human papillomavirus type-16 (HPV-16) major transforming proteins functionally interact with interferon signaling mechanisms

Perea, Silvio E.; López-Ocejo, Omar; vonGabain, A; Araña, M.J.

doi:10.3892/ijo.11.1.169

Cited by 9 publications

(6 citation statements)

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“…E7 also inhibits IRF1 DNA binding activity (Perea, Massimi et al 2000) and suppresses the upregulation of IRF1 levels in response to IFNγ (Zhou, Chen et al 2013). E6 and E7 both prevent upregulation of the IRF-dependent IFNβ promoter by infection with other viruses or by IFNγ (Perea, Lopezocejo et al 1997), but whether this is through IRF1 or other IRFs is not clear. In addition to inhibiting IRF1-mediated transactivation directly, E7 can interfere with signals that activate IRFs.…”

Section: Transcription Factors Regulated By E7mentioning

confidence: 99%

“…HPV31 E7 can suppress STAT1 at the transcriptional level, resulting in reduced IFN-mediated gene expression (Hong, Mehta et al 2011). HPV16 E7 inhibits IFN-induced phosphorylation and nuclear translocation of STAT1 and downstream expression of ISGs (Perea, Lopezocejo et al 1997; Nees, Geoghegan et al 2001; Zhou, Chen et al 2013; Zhou, Chen et al 2013). In addition to targeting STAT1 itself, HPV18 E7 can bind to the IRF9 subunit of the ISGF3 complex and prevent translocation to the nucleus (Barnard and McMillan 1999; Antonsson, Payne et al 2006).…”

Section: Transcription Factors Regulated By E7mentioning

confidence: 99%

“…E7 can also inhibit upstream signaling pathways, reducing the function of other transcription factors, including STAT1, NFκB, SMAD2/3, and IRF1 (Perea, Lopezocejo et al 1997; Mi, Borger et al 2000; Nees, Geoghegan et al 2001; Spitkovsky, Hehner et al 2002; Murvai, Borbely et al 2004; Hypes, Pirisi et al 2009; Li, Zhan et al 2009; Vandermark, Deluca et al 2012; Hasan, Zannetti et al 2013; Zhou, Chen et al 2013; Zhou, Chen et al 2013; Lau, Gray et al 2015). E7 can interfere with nuclear localization of STAT1 and NFκB (Perea, Lopezocejo et al 1997; Nees, Geoghegan et al 2001; Spitkovsky, Hehner et al 2002; Li, Zhan et al 2009; Zhou, Chen et al 2013; Zhou, Chen et al 2013). E7 can directly bind to and stimulate transcription factors, including E2F1, B-Myb, c-Myc, and c-Jun (Antinore, Birrer et al 1996; Hwang, Lee et al 2002; Wang, Chang et al 2007; Pang, Toh et al 2014).…”

Section: Figurementioning

confidence: 99%

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The human papillomavirus E7 oncoprotein as a regulator of transcription

2017

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High-risk human papillomaviruses (HPVs) encode oncoproteins which manipulate gene expression patterns in the host keratinocytes to facilitate viral replication, regulate viral transcription, and promote immune evasion and persistence. In some cases, oncoprotein-induced changes in host cell behavior can cause progression to cancer, but a complete picture of the functions of the viral oncoproteins in the productive HPV life cycle remains elusive. E7 is the HPV-encoded factor most responsible for maintaining cell cycle competence in differentiating keratinocytes. Through interactions with dozens of host factors, E7 has an enormous impact on host gene expression patterns. In this review, we will examine the role of E7 specifically as a regulator of transcription. We will discuss mechanisms of regulation of cell cycle-related genes by E7 as well as genes involved in immune regulation, growth factor signaling, DNA damage responses, microRNAs, and others pathways. We will also discuss some unanswered questions about how transcriptional regulation by E7 impacts the biology of HPV in both benign and malignant conditions.

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Section: Transcription Factors Regulated By E7mentioning

confidence: 99%

Section: Transcription Factors Regulated By E7mentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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The human papillomavirus E7 oncoprotein as a regulator of transcription

2017

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“…IFNhas been shown to signal through the type I IFN receptor and to promote the upregulation of ISGs that can then promote antiviral immunity (42). To evade IFN responses, HPV oncoproteins repress both basal and agonist-induced transcription of IFNs and ISGs (43)(44)(45)(46)(47)(48)(49)(50)(51). IFN-, in particular, seems to be a target of HPV both in vivo (52) and in cell culture (11,53,54).…”

mentioning

confidence: 99%

Human Papillomavirus 16 E5 Inhibits Interferon Signaling and Supports Episomal Viral Maintenance

Scott

Woodby

Ulicny

et al. 2020

J Virol

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Human papillomaviruses (HPVs) infect keratinocytes of stratified epithelia. Long-term persistence of infection is a critical risk factor for the development of HPV-induced malignancies. Through the actions of its oncogenes, HPV evades host immune responses to facilitate its productive life cycle. In this work, we discovered a previously unknown function of the HPV16 E5 oncoprotein in the suppression of interferon (IFN) responses. This suppression is focused on keratinocyte-specific IFN-κ and is mediated through E5-induced changes in growth factor signaling pathways, as identified through phosphoproteomics analysis. The loss of E5 in keratinocytes maintaining the complete HPV16 genome results in the derepression of IFNK transcription and subsequent JAK/STAT-dependent upregulation of several IFN-stimulated genes (ISGs) at both the mRNA and protein levels. We also established a link between the loss of E5 and the subsequent loss of genome maintenance and stability, resulting in increased genome integration. IMPORTANCE Persistent human papillomavirus infections can cause a variety of significant cancers. The ability of HPV to persist depends on evasion of the host immune system. In this study, we show that the HPV16 E5 protein can suppress an important aspect of the host immune response. In addition, we find that the E5 protein is important for helping the virus avoid integration into the host genome, which is a frequent step along the pathway to cancer development.

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“…E7 has also been demonstrated to activate the AP-1 family of transcription factors through direct interaction with the carboxyl terminus of E7 (Antimore et al, 1996). Recent studies have also suggested that E6 and E7 may interfere with the cellular response to interferon (IFN) through suppression of IFN-inducible genes (Arany et al, 1995;Perea et al, 1997). Use of yeast two-hybrid screening will undoubtedly continue to provide new potential interactors of the HPV E7 proteins such as S4 subunit of the 26S proteasome (Berezutskaya & Bagchi, 1997) and the human homologue of the Drosophila tumour suppressor protein, Tid56 (Schilling et al, 1998).…”

Section: E7 Oncoproteinmentioning

confidence: 99%

Molecular Targets for Human Papillomaviruses: Prospects for Antiviral Therapy

Phelps

Barnes

Lobe

1998

Antivir Chem Chemother

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A substantial medical need exists for the development of antiviral medicines for the treatment of diseases associated with infection by human papillomaviruses (HPVs). HPVs are associated with various benign and malignant lesions including benign genital condyloma, common skin warts, laryngeal papillomas and anogenital cancer. Since treatment options are limited and typically not very satisfactory, the development of safe and effective antiviral drugs for HPV could have substantial clinical impact. In the last few years, exciting advances have been made in our understanding of papillomavirus replication and the effects that the virus has on growth of the host cell. Although still somewhat rudimentary, techniques have been developed for limited virion production in vitro offering the promise of more rapid advances in the dissection and understanding of the virus life cycle. Of the 8–10 HPV gene products that are made during infection, only one encodes enzymatic activities, the E1 helicase. Successful antiviral therapies have traditionally targeted viral enzymes such as polymerases, kinases and proteases. In contrast, macromolecular interactions which mediate the functions of E6, E7 and E2 are thought to be more difficult targets for small molecule therapy.

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Human papillomavirus type-16 (HPV-16) major transforming proteins functionally interact with interferon signaling mechanisms

Cited by 9 publications

References 0 publications

The human papillomavirus E7 oncoprotein as a regulator of transcription

The human papillomavirus E7 oncoprotein as a regulator of transcription

Human Papillomavirus 16 E5 Inhibits Interferon Signaling and Supports Episomal Viral Maintenance

Molecular Targets for Human Papillomaviruses: Prospects for Antiviral Therapy

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