Papillomavirus E5: the smallest oncoprotein with many functions

Papillomaviruses (PVs) are established agents of human and animal cancers. They infect cutaneous and mucous epithelia. High Risk (HR) Human PVs (HPVs) are consistently associated with cancer of the uterine cervix, but are also involved in the etiopathogenesis of other cancer types. The early oncoproteins of PVs: E5, E6 and E7 are known to contribute to tumour progression. While the oncogenic activities of E6 and E7 are well characterised, the role of E5 is still rather nebulous. The widespread causal association of PVs with cancer makes their study worthwhile not only in humans but also in animal model systems. The Bovine PV (BPV) system has been the most useful animal model in understanding the oncogenic potential of PVs due to the pivotal role of its E5 oncoprotein in cell transformation. This review will highlight the differences between HPV-16 E5 (16E5) and E5 from other PVs, primarily from BPV. It will discuss the targeting of E5 as a possible therapeutic agent

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

Congenital cutaneous fibropapillomatosis in a warmblood foal

In this report, clinical and histological findings of a rare case of a large congenital fibropapilloma on the forehead of a warmblood foal are reported. Surgical excision was curative and no recurrence was observed after nine months. The foal did not present any other abnormalities. Morphologically, the lesion was classified as a fibro-epithelial type of skin hamartoma. The fibrous component has thus far only been reported in pigs. Although fibropapillomas are common in adult animals and are associated with papillomavirus infection, this association has not been demonstrated in foals and piglets. Additionally, there were no histopathological indications of papillomavirus infection in the present study, nor could PCR reveal the presence of papillomavirus DNA

HPV vaccination of immunocompromised hosts.

It is well-established that immunocompromised people are at increased risk of HPV-related disease compared with those who are immunocompetent. Prophylactic HPV sub-unit vaccines are safe and immunogenic in immunocompromised people and it is strongly recommended that vaccination occur according to national guidelines. When delivered to immunocompromised populations, HPV vaccines should be given as a 3-dose regimen

History of Cervical Cancer and the Role of the Human Papillomavirus, 1960-2000

Annotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCL. First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2009. ©The Trustee of the Wellcome Trust, London, 2009. All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCLAnnotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCLAnnotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCLAnnotated and edited transcript of a Witness Seminar held on 13 May 2008. Introduction by Professor Anne M Johnson, Division of Population Health and Institute for Global Health, UCLThe history, largely untold, of the development of cervical cytology, of effective screening and its ultimate success in reducing cervical cancer incidence and mortality, and the viral cause of cervical cancer, took place within a complex social background of changing attitudes to women’s health and sexual behaviour. Dr Georges Papanicolaou’s screening method (the Pap smear) started in the US in the 1940s. It was widely used in the UK a decade later and a national programme of cervical screening was established in 1988. The association of sexually transmitted human papillomavirus (HPV) with cervical cancer was less readily accepted. The detection of HPV16 in cervical cancers at the end of the 1970s was aided by the explosion of laboratory, clinical, and public health research on new screening tests and procedures. These made possible the successful development, licensing and use of preventive vaccines against the major oncogenic HPV types, HPV16 and -18. The Witness Seminar was attended by virologists, cytologists, gynaecologists, epidemiologists and others and addressed the development of cytology as a pathological discipline. They discussed who became cytologists and screeners; the evolution of screening in the UK and elsewhere; the impacts of colposcopy and of HPV; and the discovery of virus-like particles and the development of the HPV vaccine. The meeting was chaired by Professor Glenn McCluggage and the topic was suggested by Professor David Jenkins. Contributors include: Professor Valerie Beral, Professor Saveria Campo, Professor Jocelyn Chamberlain, Professor Dulcie Coleman, Dr Lionel Crawford, Professor Heather Cubie, Professor Jack Cuzick, Dr Ian Duncan, Dr Winifred Gray, Dr Amanda Herbert, Professor David Jenkins, Dr Elizabeth Mackenzie, Dr Joan Macnab, Professor Anthony Miller, Professor Julian Peto, Dr Catherine Pike, Professor Peter Sasieni, Professor Albert Singer, Dr John Smith, Professor Margaret Stanley, Mrs Marilyn Symonds, Dr Anne Szarewski, Professor Leslie Walker, Mr Patrick Walker, Dr Margaret Wolfendale and Professor Ciaran Woodman. Two appendices with reminiscences from Professor Leopold Koss, Dr Arthur Spriggs and Dr O A N (Nasseem) Husain complete the volume. Reynolds L A, Tansey E M. (eds) (2009) History of cervical cancer and the role of human papillomavirus, 1960–2000, Wellcome Witnesses to Twentieth Century Medicine, vol. 38. London: The Wellcome Trust Centre for the History of Medicine at UCL. ISBN 978 085484 1233The Wellcome Trust Centre for the History of MedicineMat UCL is funded by the Wellcome Trust, which is a registered charity, no. 210183

Keratinocyte differentiation-dependent human papillomavirus gene regulation

Human papillomaviruses (HPVs) cause diseases ranging from benign warts to invasive cancers. HPVs infect epithelial cells and their replication cycle is tightly linked with the differentiation process of the infected keratinocyte. The normal replication cycle involves an early and a late phase. The early phase encompasses viral entry and initial genome replication, stimulation of cell division and inhibition of apoptosis in the infected cell. Late events in the HPV life cycle include viral genome amplification, virion formation, and release into the environment from the surface of the epithelium. The main proteins required at the late stage of infection for viral genome amplification include E1, E2, E4 and E5. The late proteins L1 and L2 are structural proteins that form the viral capsid. Regulation of these late events involves both cellular and viral proteins. The late viral mRNAs are expressed from a specific late promoter but final late mRNA levels in the infected cell are controlled by splicing, polyadenylation, nuclear export and RNA stability. Viral late protein expression is also controlled at the level of translation. This review will discuss current knowledge of how HPV late gene expression is regulated

Felis catus papillomavirus type 2 infection and skin cancer in domestic cats : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Manawatū, New Zealand

Felis catus papillomavirus type 2 (FcaPV-2) is a virus which commonly infects the skin of domestic cats. While most infections are asymptomatic, there is growing evidence that FcaPV-2 may play a role in the development of a subset of feline cutaneous squamous cell carcinomas (SCCs). In the first part of this thesis, the natural history of FcaPV-2 infection was investigated with the aim of determining when cats become infected with the virus. A real-time PCR assay was developed to quantify FcaPV-2 DNA in feline skin swabs. This assay was then used to measure the FcaPV-2 DNA load in serial samples from two populations of cats. Results from these studies showed that most kittens are exposed to FcaPV-2 in the first few days of life. Additionally, the primary source of exposure is likely to be direct contact with other cats in the household, particularly their queen, as some of the queens appeared to be shedding large amounts of virus. FcaPV-2 mRNA was also detected in some of the kittens, confirming that they had become infected with FcaPV-2 soon after birth. The aim of the second part of this thesis was to determine the quantity and transcriptional activity of the FcaPV-2 DNA present in feline cutaneous SCCs in order to determine if the virus was involved in cancer development or just present as an innocent bystander. Real-time PCR assays were developed to measure FcaPV-2 gene expression in SCCs and the results clearly distinguished two subsets of feline cutaneous SCCs. The majority of the SCCs had low copy numbers of FcaPV-2 DNA and no FcaPV-2 gene expression, suggesting the virus was an incidental finding. In contrast, around a third of the SCCs had detectable FcaPV-2 gene expression and high copy numbers of FcaPV-2 DNA, similar to that found in the FcaPV-2-induced premalignant lesions. There was also a significant association between FcaPV-2 gene expression and alterations in a host cell cycle regulatory protein (p16). Taken together, these results strongly suggest that FcaPV-2 played a role in the development of around a third of the feline cutaneous SCCs. The results from the studies reported in this thesis support a causative role of FcaPV-2 in a proportion of feline cutaneous SCCs. However, as infection of cats is common and appears to occur early in life, there may be little opportunity to prevent SCC development by preventing FcaPV-2 infection

Human papillomavirus vaccination coverage in Luxembourg : implications of lowering and restricting target age groups

Background: In Luxembourg, a national Human Papillomavirus (HPV) vaccination programme was introduced in 2008, targeting 12-17 year old girls offering a choice of bivalent or quadrivalent vaccine free of charge. In 2015, the programme was changed offering the bivalent vaccine only to 11-13 year old girls. The aim of this study was to evaluate the HPV vaccination coverage, to assess the impact of age target changes and compare vaccination coverage to other European countries. Methods: Anonymous HPV vaccination records consisting of individual vaccine doses obtained free of charge in pharmacies between 2008 and 2016 were extracted from the Luxembourgish Social Security database. Additional aggregate tables by nationality and municipality were analysed. Results: Of the target cohort of 39,610 girls born between 1991 and 2003 residing in Luxembourg, 24,550 (62.0%) subjects obtained at least one dose, 22,082 (55.7%) obtained at least two doses, and 17,197 (43.4%) obtained three doses of HPV vaccine. The mean age at first dose was 13.7 years during 200814 and 12.7 years in 2016 after the age target change. Coverage varied significantly by nationality (p < 0.0001): Portuguese (80%), former Yugoslays (74%), Luxembourgish (54%), Belgian (52%), German (47%), French (39%) and other, nationalities (51%). Coverage varied also by geographical region, with lower rates (<50%) noted in some Northern and Central areas of Luxembourg (range: 38% to 78%). Conclusion: Overall HPV vaccination coverage in Luxembourg is moderate and varied by nationality and region. The policy changes in 2015 did not have a substantial impact except lowering age at initiating vaccination. Options to improve coverage deserve further investigation

Bovine papillomavirus: old system, new lessons?

No abstract available

Control of human papillomavirus gene expression by alternative splicing

Human papillomaviruses possess circular double stranded DNA genomes of around 8 kb in size from which multiple mRNAs are synthesized during an infectious life cycle. Although at least three viral promoters are used to initiate transcription, viral mRNAs are largely the product of processing of pre-mRNAs by alternative splicing and polyadenylation. The HPV life cycle and viral gene expression are tightly linked to differentiation of the epithelium the virus infects: there is an orchestrated production of viral mRNAs and proteins. In this review we describe viral mRNA expression and the roles of the SR and hnRNP proteins that respectively positively and negatively regulate splicing. We discuss HPV regulation of splicing factors and detail the evidence that the papillomavirus E2 protein has splicing-related activities. We highlight the possibility that HPV-mediated control of splicing in differentiating epithelial cells may be necessary to accomplish the viral replication cycle