The human papillomavirus (HPV)-related cancer biology: An overview (original) (raw)
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International Journal of Cancer, 1996
The frequent association of human papillomaviruses (HPV) with invasive carcinoma of the uterine cervix, which is one of the leading causes of cancer-related mortality among women world-wide, indicates a crucial role for papillomaviruses in the development of anogenital cancer . HPVl6 is the most prevalent type of a group of "high-risk" HPVs that are predominantly found in high-grade intra-epithelial neoplasias and cervical carcinomas, while "low-risk '' types, like HPV6 and 11, are mainly associated with benign tumours but rarely with malignancies (reviewed in Walboomers et al., 1994). A large number of studies relate the activity of the viral gene products E6 and E7 to carcinogenesis. The genomic region encoding E6 and E7 is specifically retained in HPVpositive cancers (Smotkin and Wettstein, 1986; Shirasawa et al., 1987;, and the expression of both oncoproteins was shown to be necessary for the continuous growth of HPV-positive cell lines (von Knebel Doeberitz et al., 1992). Furthermore, the E6 and E7 proteins of high-risk genital HPVs are able to transform rodent cell lines, and both proteins cooperate in the immortalization of primary keratinocytes, which are the natural target cells of the virus (Tomma-sin0 and Crawford, 1995; Miinger et al., 1989). The carcinogenic potential of the E6 and E7 proteins of genital papillomaviruses correlates with their capability to bind to the tumour-suppressor proteins p53 and pRB, respectively; these interactions affect important control functions of the tumoursuppressor proteins in the cell cycle (reviewed in Huibregtse and Schefier, 1994). Three different transcripts derived from the E6/E7region have been described for the high-risk HPV16 which are generated by a common promoter (P97) located up-stream of the E6 O W . The activity of the early promoter P97 is regulated by a series of cis-elements in the non-coding region (NCR), in particular by an epithelial cell-specific enhancer core of at least 232 bp which contains multiple, closely spaced binding sites for ubiquitous transcription factors . In addition, the NCR contains 4 palindromic recognition sites for the viral transcription factor E2, which is an important negative regulator of P97 activity and, therefore, of expression of the viral oncogenes E6 and E7 (Romanczuk et al., 1990; Tan et al., 1992).
International journal of oncology, 2018
Human papilloma viruses (HPV) are a small group of non‑enveloped viruses belonging to the Papillomaviridae family with strong similarities to polyoma viruses. The viral particles consist of a genome in the form of a circular double‑stranded DNA, encompassing eight open reading frames, as well as a non‑enveloped icosahedral capsid. HPV infection is considered the most common sexually transmitted disease in both sexes and is strongly implicated in the pathogenesis of different types of cancer. 'High‑risk' mucosal HPV types, predominantly types 16, 18, 31, 33 and 35, are associated with most cervical, penile, vulvar, vaginal, anal, oropharyngeal cancers and pre‑cancers. Screening for HPV is necessary for the prognosis and for determining treatment strategies for cancer. Novel HPV markers, including proteomic and genomic markers, as well as anti‑papillomavirus vaccines are currently available. The aim of this comprehensive review was to thoroughly present the updated information...
International Journal of Molecular Sciences
Human papillomavirus (HPV) is a group of alpha papillomaviruses that cause various illnesses, including cancer. There are more than 160 types of HPV, with many being “high-risk” types that have been clinically linked to cervical and other types of cancer. “Low-risk” types of HPV cause less severe conditions, such as genital warts. Over the past few decades, numerous studies have shed light on how HPV induces carcinogenesis. The HPV genome is a circular double-stranded DNA molecule that is approximately 8 kilobases in size. Replication of this genome is strictly regulated and requires two virus-encoded proteins, E1 and E2. E1 is a DNA helicase that is necessary for replisome assembly and replication of the HPV genome. On the other hand, E2 is responsible for initiating DNA replication and regulating the transcription of HPV-encoded genes, most importantly the E6 and E7 oncogenes. This article explores the genetic characteristics of high-risk HPV types, the roles of HPV-encoded protei...
Cervical cancer incidence remains highly frequent in developing countries. It is possible that populations of these countries are exposed to more oncogenic human papillomavirus (HPV) variants. Functional differences among high-risk HPV variants have been described, suggesting repercussions on their oncogenic potential. In this report, we demonstrate that the long control region (LCR) of HPV18 variants has distinct transcriptional activities in different cervical cancer cell lines. African (Af)-LCR possessed the lowest transcriptional activity; its sequence harbors the highest number of nucleotide changes among the HPV18 variants analyzed. Some of these embedded in identified transcription-factor-binding sites, suggesting a less aggressive biological activity possibly involved in a slower progression of cervical lesions. Asian- Amerindian LCR showed distinct activities among cell types, while European LCR activity was similar in cell lines tested. Despite multiple nucleotide substitutions found in HPV18 E2 variant genes, their repressive activities over homologous LCRs were not distinct among variants.
Journal of Virology, 2014
Betapapillomavirus replication and transcription have not been studied in detail because of a lack of suitable cellular systems supporting human papillomavirus (HPV) genome replication. We have recently shown that the human osteosarcoma cell line U2OS provides a useful environment for the genome replication of many different HPVs, including the betapapillomaviruses HPV5 and HPV8. Using mutational analysis and complementation assay, we demonstrated herein that the viral early proteins E1 and E2 are viral transfactors that are necessary and sufficient for HPV5 genome replication. We also identified four HPV5 early promoter regions with transcription start sites (TSSs) at nucleotides (nt) 184/191, 460, 840, and 1254, respectively, and the HPV late promoter with a TSS at nt 7640. In addition, we mapped the HPV5 early polyadenylation cleavage sites via 3= rapid amplification of cDNA ends (3=RACE) to nt 4457 and 4475. In total, 14 different viral mRNA species, originating from the HPV5 genome, were mapped in U2OS cells during transient and stable replication. The main splicing donor and acceptor sites identified herein are consistent with the data previously obtained in HPV5-positive skin lesions. In addition, we identified novel E8 open reading frame (ORF)-containing transcripts (E8^E1C and E8^E2C) expressed from the HPV5 genome. Similar to several other papillomaviruses, the product of the E8^E2C mRNA acts as a repressor of viral genome replication.
The Biology and Life-Cycle of Human Papillomaviruses
Vaccine, 2012
Human papillomaviruses (HPVs) comprise a diverse group, and have different epithelial tropisms and life-cycle strategies. Many HPVs are classified as low-risk, as they are only very rarely associated with neoplasia or cancer in the general population. These HPVs typically cause inapparent/inconspicuous infections, or benign papillomas, which can persist for months or years, but which are eventually resolved by the host's immune system. Low-risk HPVs are difficult to manage in immunosuppressed people and in individuals with genetic predispositions, and can give rise to papillomatosis, and in rare instances, to cancer. The high-risk HPV types are, by contrast, a cause of several important human cancers, including almost all cases of cervical cancer, a large proportion of other anogenital cancers and a growing number of head and neck tumours. The high-risk HPV types constitute a subset of the genus Alphapapillomavirus that are prevalent in the general population, and in most individuals cause only inconspicuous oral and genital lesions. Cancer progression is associated with persistent high-risk HPV infection and with deregulated viral gene expression, which leads to excessive cell proliferation, deficient DNA repair, and the accumulation of genetic damage in the infected cell. Although their life-cycle organisation is broadly similar to that of the low-risk HPV types, the two groups differ significantly in their capacity to drive cell cycle entry and cell proliferation in the basal/parabasal cell layers. This is thought to be linked, at least in part, to different abilities of the high-and low-risk E6 proteins to modulate the activity of p53 and PDZ-domain proteins, and the differential ability of the E7 proteins to target the several different members of the retinoblastoma protein family. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and
Human Papillomavirus Oncogenesis: A Narrative Review
Caliphate Medical Journal, 2021
Human papillomavirus (HPV) is a member of the Papillomaviridae family which infects squamous cells and mucous layers of humans. Cancer-causing expression of high-risk HPV-infected cells is an unsuccessful, terminal occasion since most disease cells contain incorporated HPV genomes and do create virus descendants. If the reconciliation of high-risk HPV genomes without a doubt addresses an outcome of HPV E6/E7-incited genomic instability, it gives the idea that such a replication procedure may put high-risk HPVs in a difficult situation contrasted with the generally low-risk HPVs that infect the anogenital mucosa. Low-risk HPV E6 and E7 proteins add to the virus life cycle; however they have a significantly lower changing expression and do not incite genomic instability. Low-risk HPV E7 proteins tie to pRB at a diminished proficiency and do not instigate pRB destabilization. HPV E6 proteins don't proficiently communicate with p53 and are uncouth for p53 debasement. High-risk HPVs ...
HUMAN PAPILLOMAVIRUS BIOLOGY: REVIEW
Journal of Advanced Research
Sexually transmitted infections (STIs) are more dynamic than any other diseases in both developing and developed countries. Human Papillomaviruses (HPVs) are icosahedral, small, non-enveloped particle measuring ~55 nm in diameter. They are ~8000 base-pair (bp), double stranded circular DNA molecule which wrapped into a protein shell by two molecules namely, L1 and L2. The HPV genome has the coding capacity for two late proteins (L1 and L2) and for six early proteins (E1, E2, E4–E7) which are necessary for the replication of the viral DNA and for the assembly of newly produced virus particles within the infected cells. More than 100 HPV types have been characterized molecularly and about 40 types are able to infect the epithelial lining of the anogenital tract and other mucosal areas of the human body. Human papillomavirus (HPV) is a necessary cause of cervical, anogenital, upper aerodigestive tract and skin cancers. Other cofactors are necessary for progression from cervical HPV inf...