Aberrant Splicing Events and Epigenetics in Viral Oncogenomics: Current Therapeutic Strategies

Francies, Flavia Zita; Dlamini, Zodwa

doi:10.3390/cells10020239

Cited by 14 publications

(19 citation statements)

References 114 publications

(197 reference statements)

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“…Thus, the vIL-8 splice variants could potentially play roles in MDV-induced disease and tumor formation. Moreover, virus-encoded splice variants in general have been found to inhibit tumor suppressors, evade an immune response, and promote tumorigenesis [ 35 , 36 ]. To assess the effect of the novel splice variant on MDV pathogenesis, we infected one-day-old chickens with a virus that does not express the new vIL-8 splice variant.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Novel Viral Interleukin 8 (vIL-8) Splice Variant Encoded by Marek’s Disease Virus

et al. 2021

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Marek’s disease virus (MDV) is a highly cell-associated oncogenic alphaherpesvirus that causes lymphomas in various organs in chickens. Like other herpesviruses, MDV has a large and complex double-stranded DNA genome. A number of viral transcripts are generated by alternative splicing, a process that drastically extends the coding capacity of the MDV genome. One of the spliced genes encoded by MDV is the viral interleukin 8 (vIL-8), a CXC chemokine that facilitates the recruitment of MDV target cells and thereby plays an important role in MDV pathogenesis and tumorigenesis. We recently identified a novel vIL-8 exon (vIL-8-E3′) by RNA-seq; however, it remained elusive whether the protein containing the vIL-8-E3′ is expressed and what role it may play in MDV replication and/or pathogenesis. To address these questions, we first generated recombinant MDV harboring a tag that allows identification of the spliced vIL-8-E3′ protein, revealing that it is indeed expressed. We subsequently generated knockout viruses and could demonstrate that the vIL-8-E3′ protein is dispensable for MDV replication as well as secretion of the functional vIL-8 chemokine. Finally, infection of chickens with this vIL-8-E3′ knockout virus revealed that the protein is not important for MDV replication and pathogenesis in vivo. Taken together, our study provides novel insights into the splice forms of the CXC chemokine of this highly oncogenic alphaherpesvirus.

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Section: Discussionmentioning

confidence: 99%

Characterization of a Novel Viral Interleukin 8 (vIL-8) Splice Variant Encoded by Marek’s Disease Virus

et al. 2021

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“…The E1 , E2 , and E4 genes are involved in HPV viral replication, while the remaining three non-structural genes E5 , E6 , and E7 are involved in HPV viral-induced cellular transformation [ 20 , 21 ]. High-risk HPV 16 and 18 infections are responsible for most cervical cancer cases [ 22 , 23 ]. Most HPV infections are cleared through surveillance by the immune system.…”

Section: Human Papillomaviruses (Hpv)mentioning

confidence: 99%

Viral Encoded miRNAs in Tumorigenesis: Theranostic Opportunities in Precision Oncology

et al. 2022

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About 15% of all human cancers have a viral etiology. Although progress has been made, understanding the viral oncogenesis and associated molecular mechanisms remain complex. The discovery of cellular miRNAs has led to major breakthroughs. Interestingly, viruses have also been discovered to encode their own miRNAs. These viral, small, non-coding miRNAs are also known as viral-miRNAs (v-miRNAs). Although the function of v-miRNAs largely remains to be elucidated, their role in tumorigenesis cannot be ignored. V-miRNAs have also been shown to exploit the cellular machinery to benefit viral replication and survival. Although the discovery of Hepatitis C virus (HCV), and its viral miRNAs, is a work in progress, the existence of HPV-, EBV-, HBV-, MCPyV- and KSHV-encoded miRNA has been documented. V-miRNAs have been shown to target host factors to advance tumorigenesis, evade and suppress the immune system, and deregulate both the cell cycle and the apoptotic machinery. Although the exact mechanisms of v-miRNAs-induced tumorigenesis are still unclear, v-miRNAs are active role-players in tumorigenesis, viral latency and cell transformation. Furthermore, v-miRNAs can function as posttranscriptional gene regulators of both viral and host genes. Thus, it has been proposed that v-miRNAs may serve as diagnostic biomarkers and therapeutic targets for cancers with a viral etiology. Although significant challenges exist in their clinical application, emerging reports demonstrate their potent role in precision medicine. This review will focus on the roles of HPV-, HCV-, EBV-, HBV-, MCPyV-, and KSHV-produced v-miRNAs in tumorigenesis, as effectors in immune evasion, as diagnostic biomarkers and as novel anti-cancer therapeutic targets. Finally, it will discuss the challenges and opportunities associated with v-miRNAs theranostics in precision oncology.

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“…With some geographical variation, HPV infection causes 70% of cancers of the vulva, 75% of all vaginal cancers, 60% of all penile cancers, 90% of all anal cancers and 70% of all oropharyngeal cancers. In terms of cervical cancer, it is thought that nearly all cervical cancers are caused by persistent HPV infection [ 3 , 26 ].…”

Section: Hpv-related Cancersmentioning

confidence: 99%

The Catastrophic HPV/HIV Dual Viral Oncogenomics in Concert with Dysregulated Alternative Splicing in Cervical Cancer

Marima

Hull

Lolas

et al. 2021

IJMS

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Cervical cancer is a public health problem and has devastating effects in low-to-middle-income countries (LTMICs) such as the sub-Saharan African (SSA) countries. Infection by the human papillomavirus (HPV) is the main cause of cervical cancer. HIV positive women have higher HPV prevalence and cervical cancer incidence than their HIV negative counterparts do. Concurrent HPV/HIV infection is catastrophic, particularly to African women due to the high prevalence of HIV infections. Although various studies show a relationship between HPV, HIV and cervical cancer, there is still a gap in the knowledge concerning the precise nature of this tripartite association. Firstly, most studies show the relationship between HPV and cervical cancer at genomic and epigenetic levels, while the transcriptomic landscape of this relationship remains to be elucidated. Even though many studies have shown HPV/HIV dual viral pathogenesis, the dual molecular oncoviral effects on the development of cervical cancer remains largely uncertain. Furthermore, the effect of highly active antiretroviral therapy (HAART) on the cellular splicing machinery is unclear. Emerging evidence indicates the vital role played by host splicing events in both HPV and HIV infection in the development and progression to cervical cancer. Therefore, decoding the transcriptome landscape of this tripartite relationship holds promising therapeutic potential. This review will focus on the link between cellular splicing machinery, HPV, HIV infection and the aberrant alternative splicing events that take place in HIV/HPV-associated cervical cancer. Finally, we will investigate how these aberrant splicing events can be targeted for the development of new therapeutic strategies against HPV/HIV-associated cervical cancer.

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Aberrant Splicing Events and Epigenetics in Viral Oncogenomics: Current Therapeutic Strategies

Cited by 14 publications

References 114 publications

Characterization of a Novel Viral Interleukin 8 (vIL-8) Splice Variant Encoded by Marek’s Disease Virus

Characterization of a Novel Viral Interleukin 8 (vIL-8) Splice Variant Encoded by Marek’s Disease Virus

Viral Encoded miRNAs in Tumorigenesis: Theranostic Opportunities in Precision Oncology

The Catastrophic HPV/HIV Dual Viral Oncogenomics in Concert with Dysregulated Alternative Splicing in Cervical Cancer

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