Human papillomavirus E6 and E7: What remains?

Vats, Arushi; Trejo-Cerro, Óscar; Thomas, Miranda; Banks, Lawrence

doi:10.1016/j.tvr.2021.200213

Cited by 58 publications

(68 citation statements)

References 291 publications

(235 reference statements)

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“…Excellent vaccines are the keys to prevent initial infection; however, as discussed earlier, for cases of persistent infection there is a likelihood of development of cancer and malignancy over several years, orchestrated by expression of E5, E6 and E7—the not-so-good, the bad and the ugly—in terms of their molecular prognosis/outcome, as discussed above. Despite a multitude of data regarding the mechanisms behind the carcinogenic effects of these viral oncoproteins, many mechanisms still remain to be uncovered (refer to review [ 375 ]), and specific therapeutic agents against HPV-mediated cancer have not yet been found. However, ongoing clinical trials of promising therapeutic agents against specific targets, and more studies further elucidating the mechanisms of carcinogenic orchestration by these oncoproteins, will eventually aid in the development of therapy against HPV-mediated disease and carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis

Basukala

Banks

2021

Viruses

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Infection with HPV starts with the access of the viral particles to basal cells in the epidermis, potentially via microtraumas to the skin. The basal cells are able to keep away these pathogens in normal circumstances through a robust immune response from the host, as HPV infections are, in general, cleared within 2 to 3 weeks. However, the rare instances of persistent infection and/or in cases where the host immune system is compromised are major risk factors for the development of lesions potentially leading to malignancy. Evolutionarily, obligatory pathogens such as HPVs would not be expected to risk exposing the host to lethal cancer, as this would entail challenging their own life cycle, but infection with these viruses is highly correlated with cancer and malignancy—as in cancer of the cervix, which is almost always associated with these viruses. Despite this key associative cause and the availability of very effective vaccines against these viruses, therapeutic interventions against HPV-induced cancers are still a challenge, indicating the need for focused translational research. In this review, we will consider the key roles that the viral proteins play in driving the host cells to carcinogenesis, mainly focusing on events orchestrated by early proteins E5, E6 and E7—the not-so-good, the bad and the ugly—and discuss and summarize the major events that lead to these viruses mechanistically corrupting cellular homeostasis, giving rise to cancer and malignancy.

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Section: Discussionmentioning

confidence: 99%

The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis

Basukala

Banks

2021

Viruses

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“…The current study, an extension of our earlier work, is aimed at identifying the distinctive features of HPV16 lineages among SCC cases from the eastern region of India, with respect to genomic variations, viral DNA load and E7 expression as markers of oncogenicity. Among the two major oncoproteins, E7 over E6 was chosen because of least variability in CaCx [32] , role in initiation of the quasi-S phase essential for viral genome replication in differentiated epithelial cells [33] , and presence of higher number of HPV16 E7 transcripts in cancers in contrast to HPV18 cancers [34] .…”

Section: Introductionmentioning

confidence: 99%

Predominance of genomically defined A lineage of HPV16 over D lineage in Indian patients from eastern India with squamous cell carcinoma of the cervix in association with distinct oncogenic phenotypes

Mandal

Bhattacharjee

Sen

et al. 2022

Translational Oncology

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“…Among the many activities elicited by E6 and E7, their respective interactions with p53 and pRB are crucial for immortalization. In addition, these oncoproteins have many more activities and interact with a plethora of cellular factors with far reaching consequences not only for the virus life cycle, but also for transformation (see for example : Neveu et al 2012;Poirson et al 2017;Vats et al 2021). Figure 4 shows some of the key interactions of E6 and E7 with cellular components that are important for immortalization and cancer development, highlighting in particular those that are most relevant to the areas discussed in this paper.…”

Section: The Hpv E6 and E7 Oncoproteins And Their Interactions With Cellular Componentsmentioning

confidence: 99%

Human papillomavirus-mediated carcinogenesis and tumor progression

Abboodi

Delva

Emmel

et al. 2021

GENOME INSTAB. DIS.

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High-risk human papillomaviruses (HPV) cause 5% of all human cancers and are primary etiologic agents of cervical, anal, and oropharyngeal cancer. HPV infection is necessary, but not sufficient per se to produce cancer: additional changes must occur that transform HPV-infected cells to malignancy. The HPV oncoproteins E6 and E7 immortalize human keratinocytes, cervical cells, and fibroblasts in culture. Each oncoprotein interacts with a variety of cellular binding partners; most important for transformation are E6 and E7's interactions with p53 and RB (respectively) which lead to degradation of p53 and RB through the ubiquitin pathway. Inactivation of p53 and RB leads to inactivation of pivotal cell cycle checkpoints, thereby stimulating cell proliferation and allowing cell division to occur independently of the presence of DNA damage, replicative stress, and other such insults, leading to genome instability. Continuous expression of E6/E7 drives the proliferation and progression of most HPV-mediated cancers of the cervix and a substantial fraction of those of the oropharynx. However, at both cancer sites, "HPV-inactive" tumors that contain HPV DNA, but do not express E6/E7 arise. We propose that these HPV-inactive cancers begin as HPV-driven lesions, but lose E6/E7 expression at some point during progression. We have recently shown that p53 deletion in HPV-immortalized, premalignant cells allows for the emergence of cell populations that no longer express E6/E7. These findings corroborate the notion of a pivotal role of p53 in the context of HPV-mediated transformation, both at the initiation and progression stages of cancer development.

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Human papillomavirus E6 and E7: What remains?

Cited by 58 publications

References 291 publications

The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis

The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis

Predominance of genomically defined A lineage of HPV16 over D lineage in Indian patients from eastern India with squamous cell carcinoma of the cervix in association with distinct oncogenic phenotypes

Human papillomavirus-mediated carcinogenesis and tumor progression

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