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Activation of p53-regulated pro-survival signals and hypoxia-independent mitochondrial targeting of TIGAR by human papillomavirus E6 oncoproteins
Virology. 2023 May 22;585:1-20. doi: 10.1016/j.virol.2023.05.004. Online ahead of print.ABSTRACTThe high-risk subtype human papillomaviruses (hrHPVs) infect and oncogenically transform basal epidermal stem cells associated with the development of squamous-cell epithelial cancers. The viral E6 oncoprotein destabilizes the p53 tumor suppressor, inhibits p53 K120-acetylation by the Tat-interacting protein of 60 kDa (TIP60, or Kat5), and prevents p53-dependent apoptosis. Intriguingly, the p53 gene is infrequently mutated in HPV + cervical cancer clinical isolates which suggests a possible paradoxical role for this gatekeeper i...
Source: Virology - May 31, 2023 Category: Virology Authors: Lacin Yapindi Tetiana Bowley Nick Kurtaneck Rachel L Bergeson Kylie James Jillian Wilbourne Carolyn K Harrod Brenda Y Hernandez Brooke M Emerling Courtney Yates Robert Harrod Source Type: research

Viruses, Vol. 14, Pages 1150: The Process of Filopodia Induction during HPV Infection
In this study, we demonstrate that after HPV16 comes into contact with a plasma membrane receptor, there are cytoskeletal changes resulting in an increase of filopodia numbers. This increase in filopodia numbers was transient and was maintained during the first two hours after virus addition. Our data show that there is a statistically significant increase in infection when filopodia numbers are increased by the addition of drug and virus simultaneously, and a decrease in virus infection when filopodia formation is inhibited. We describe that HPV16 binding results in the activation of Cdc42 GTPase that in turn results in a...
Source: Viruses - May 26, 2022 Category: Virology Authors: Alyssa Biondo Patricio I. Meneses Tags: Article Source Type: research

Viruses, Vol. 7, Pages 5243-5256: HPV16 E6 Controls the Gap Junction Protein Cx43 in Cervical Tumour Cells
Human papillomavirus type 16 (HPV16) causes a range of cancers including cervical and head and neck cancers. HPV E6 oncoprotein binds the cell polarity regulator hDlg (human homologue of Drosophila Discs Large). Previously we showed in vitro, and now in vivo, that hDlg also binds Connexin 43 (Cx43), a major component of gap junctions that mediate intercellular transfer of small molecules. In HPV16-positive non-tumour cervical epithelial cells (W12G) Cx43 localised to the plasma membrane, while in W12T tumour cells derived from these, it relocated with hDlg into the cytoplasm. We now provide evidence that E6 regulates this ...
Source: Viruses - October 5, 2015 Category: Virology Authors: Peng SunLi DongAlasdair MacDonaldShahrzad AkbariMichael EdwardMalcolm HodginsScott JohnstoneSheila Graham Tags: Article Source Type: research

DAXX modulates human papillomavirus early gene expression and genome replication in U2OS cells
Conclusions: The DAXX protein modulates the early gene expression and the transient replication of HPV genomes in U2OS cells.
Source: Virology Journal - July 7, 2015 Category: Virology Authors: Piia KivipõldLiisi VõsaMart UstavReet Kurg Source Type: research

The human papillomavirus18 E7 protein inhibits CENP-C binding to α-satellite DNA.
In this study, we first found that CENP-C could bind centromere α-satellite DNAs using ChIP analysis and HA-tagged CENP-C/nuc transfected 293T cells. We then investigated if HA-CENP-C/nuc binding to α-satellite DNAs was affected by the E7 proteins of high- or low-risk HPVs. We found that transfection of the FLAG tagged HPV 18 E7 inhibited the binding of HA-CENP-C/nuc to α-satellite DNAs. This finding was confirmed in HeLa S3 cells transfected with siRNA targeted to HPV18 E7 expression. We therefore speculate that altered function of kinetochores as a result of inhibition of CENP-C and α-satellite DNA binding may be ass...
Source: Virus Research - May 18, 2015 Category: Virology Authors: Yaginuma Y, Yoshimoto M, Eguchi A, Tokuda A, Takahashi S Tags: Virus Res Source Type: research

Depletion of polycistronic transcripts using short interfering RNAs: cDNA synthesis method affects levels of non-targeted genes determined by quantitative PCR
Conclusions: These data emphasise the importance of the cDNA synthesis method used when measuring transcript abundance following siRNA depletion of polycistronic transcripts. They provide a partial explanation for erroneous reports suggesting that siRNAs targeting HPV E7 can have gene-specific effects.
Source: Virology Journal - May 21, 2013 Category: Virology Authors: Jennifer HanningIan GrovesMark PettNicholas Coleman Source Type: research

Inhibition of cervical cancer cell growth in vitro and in vivo by lentiviral-vector mediated shRNA targeting the common promoter of HPV16 E6 and E7 oncogenes.
Abstract Deregulated expression of high-risk human papillomavirus oncogenes (E6 and E7) is a pivotal event for pathogenesis and progression in cervical cancer. Both viral oncogenes are therefore regarded as ideal therapeutic targets. Small interfering RNAs (siRNA) or double-stranded RNAs can knock down target genes effectively through siRNA-induced transcriptional gene silencing (TGS). Here, we established lentiviral-vector mediated shRNA (LV-shRNA) targeting common promoter of HPV16 E6/E7 and targeting E6 transcript, transduced the lentiviral construct into cervical HPV16-positive cell lines Siha and Caski, then ...
Source: Antiviral Research - May 1, 2013 Category: Virology Authors: Zhou J, Li B, Peng C, Wang F, Fu Z, Zhou C, Hong D, Ye F, Lü W, Xie X Tags: Antiviral Res Source Type: research