Structural Insights in Multifunctional Papillomavirus Oncoproteins

Abstract

Since their discovery in the mid-eighties, the main papillomavirus oncoproteins E6 and E7 have been recalcitrant to high-resolution structure analysis. However, in the last decade a wealth of three-dimensional information has been gained on both proteins whether free or complexed to host target proteins. Here, we first summarize the diverse activities of these small multifunctional oncoproteins. Next, we review the available structural data and the new insights they provide about the evolution of E6 and E7, their multiple interactions and their functional variability across human papillomavirus (HPV) species.

The Detection and Association of Canine Papillomavirus with Benign and Malignant Skin Lesions in Dogs

“…Usually, CPV 2 was detected from benign lesions, such as endophytic papillomas, exophytic papillomas, and, occasionally, in SCCs from immunosuppressed dogs [30,33]. These different findings might be due to differences among these CPV genomes, such as mutations in E5, E6, and E7 [16][17][18], or host immune responses. Further investigations should be performed to understand the oncogenesis of the CPVs.…”

“…Through the differentiation procedure, the early proteins (E) are generated to manipulate the host cell cycle and achieve the viral DNA replication through different ways [15]. The over-expression of E5, E6, and E7 destroys the normal cell replication cycle, disrupts the host immune response, and influences the host gene expression, thereby contributing to the cellular transformation and oncogenicity [16][17][18].…”

The Use of Both Therapeutic and Prophylactic Vaccines in the Therapy of Papillomavirus Disease

“…There are 15 high-risk (HR)-HPV genotypes that can lead to cancers of the cervix, anus, penis, vagina, vulva, and oropharynx (i.e., HPV16, 18,3,33,35,39,45,51,52,56,58,68,73,82) (7). The relevance of HPV to each of these individual cancers is now considered.…”

“…The E6 oncoprotein acts through its PDZbinding motif, which promotes its interactions with PDZ domains in multidomain proteins, to alter their functionality. These PDZ domains are present in many multidomain proteins that regulate key steps in the cellular processes of apoptosis, adhesion, and polarity (37)(38)(39)(40)(41)(42)(43)58). E6 also impairs the activity of the p53 protein, which prevents DNA damage accumulation through induction of DNA repair, cell-cycle arrest, or apoptosis, which leads to transformation of HPV chronically infected cells.…”

“…The high-risk HPV types (i.e., HPV16, 18,31,33,35,39,45,51,52,56,58,59) are considered to be the main etiological agents of genital tract cancers, such as cervical, vulvar, vaginal, penile, and anal cancers, and of a subset of head and neck cancers. Three prophylactic HPV vaccines are available that are bivalent (vs. HPV16, 18), tetravalent (vs. HPV6, 11,16,18), and non-avalent (vs. HPV6, 11,16,18,31,33,45,52,58). All of these vaccines are based on recombinant DNA technology, and they are prepared from the purified L1 protein that self-assembles to form the HPV type-specific empty shells (i.e., virus-like particles).…”