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Background Human papillomavirus type-6 (HPV6) is the major etiological agent of anogenital warts both men and women. The present study aimed to characterize the genetic diversity among HPV6 in Southwest China, and to investigate the origin of, selective pressure experienced by, and impact of the resultantly identified genetic variants on the HPV6 secondary structure. Methods Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by Molecular Evolutionary Genetics Analysis version 6.0. The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by Phylogenetic Analyses by Maximum Likelihood version 4.8 software. Results HPV6 was the most prevalent low risk HPV type in southwest China. In total, 143 E6 and E7 gene sequences of HPV6 isolated from patients were sequenced and compared to GenBank HPV6 reference sequence X00203. The results of these analyses revealed that both the HPV6 E6 and E7 were highly conserved within the analyzed patient samples, and comprised only 3 types of variant sequence, respectively. Furthermore, the analysis of HPV6 E6 and E7 sequences revealed seven/five single-nucleotide mutations, two/four and five/one of which were non-synonymous and synonymous, respectively. The phylogenetic analyses of the E6 and E7 sequences indicated that they belonged to sub-lineage A1 and sub-lineage B1, whereas the selective pressure analyses showed that only the E7 mutation sites 4R, 34E, and 52F were positive selection. Conclusions HPV6 (detection rate = 13.10%) was very prevalent in southwest China, both the HPV6 E6 and E7 sequences were highly conserved within the analyzed patient samples in southwest China, indicating that the low risk HPV6 can adapt to the environment well without much evolution.

Background. Recurrent respiratory papillomatosis (RRP) is mainly associated with human papillomavirus (HPV) 6 or HPV11. The purpose of this study was to compare clinical outcome, aggressiveness, and treatment response between HPV6- and HPV11-associated RRP.Methods. A retrospective cohort of 55 patients with RRP (1974-2012) was used. Surgical interventions (n = 814) were analyzed, and complications scored. HPV6/11-specific polymerase chain reaction (PCR) was performed on RRP biopsies.Results. Seventy-six percent of patients (42 of 55) were infected with HPV6 and 24% (13 of 55) with HPV11. The HPV11 group had anatomically more widespread disease. The expected number of surgical interventions was higher in the younger age (Conclusion. Anatomically, HPV11-associated RRP behaves more aggressively. Younger patients with HPV11 and older patients with HPV6 experience a worse clinical course of RRP. (C) 2014 Wiley Periodicals, Inc.

Background. Recurrent respiratory papillomatosis (RRP) is mainly associated with human papillomavirus (HPV) 6 or HPV11. The purpose of this study was to compare clinical outcome, aggressiveness, and treatment response between HPV6- and HPV11-associated RRP. Methods. A retrospective cohort of 55 patients with RRP (1974-2012) was used. Surgical interventions (n = 814) were analyzed, and complications scored. HPV6/11-specific polymerase chain reaction (PCR) was performed on RRP biopsies. Results. Seventy-six percent of patients (42 of 55) were infected with HPV6 and 24% (13 of 55) with HPV11. The HPV11 group had anatomically more widespread disease. The expected number of surgical interventions was higher in the younger age ( Conclusion. Anatomically, HPV11-associated RRP behaves more aggressively. Younger patients with HPV11 and older patients with HPV6 experience a worse clinical course of RRP. (C) 2014 Wiley Periodicals, Inc.

Submitted by Marina Carrara Dias null (marinacarrara@gmail.com) on 2017-03-23T23:31:58Z No. of bitstreams: 1 Dissertação de Mestrado - Marina Carrara Dias.pdf: 1359778 bytes, checksum: 1a86974bba308440e44e9b4bc3265016 (MD5) Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-03-24T16:24:52Z (GMT) No. of bitstreams: 1 dias_mc_me_sjrp_par.pdf: 509464 bytes, checksum: 6901a5ad2915883515b5407c46225a92 (MD5) Made available in DSpace on 2017-03-24T16:24:52Z (GMT). No. of bitstreams: 1 dias_mc_me_sjrp_par.pdf: 509464 bytes, checksum: 6901a5ad2915883515b5407c46225a92 (MD5) Previous issue date: 2017-03-06 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Condiloma acuminado (CA) ou verrugas genitais são lesões proliferativas benignas epidérmicas ou mucosas. O condiloma é causado pela infecção pelo papilomavírus humano (HPV), principalmente os tipos de baixo-risco 6 e 11, mas também pode ocorrer coinfecção com os HPVs de alto-risco. As variantes dos HPVs são definidas como sequências virais que compartilham identidade na sequência nucleotídica do gene L1 maior que 98%. Baseado nesse critério, linhagens de variantes de HPV6 e 11 têm sido estudadas e ainda há uma tentativa de correlacionar essas variações genéticas com os resultados clínicos diferenciais da infecção. Dessa forma, o objetivo do estudo foi detectar as variantes e alterações nucleotídicas presentes em E6 do HPV dos tipos 6 e 11 presentes em amostras de condiloma acuminado, correlacionar a presença de HPV com os dados clínico-patológicos das pacientes e determinar as relações filogenéticas das variantes encontradas com variantes de outras partes do mundo. A região E6 de 32 amostras de condiloma acuminado foi sequenciada, sendo dessas 25 positivas para HPV6 e sete para HPV11. Entre as amostras HPV6, 12 foram identificadas como a variante HPV6a, apresentando a mutação nucleotídica G474A, sendo uma delas também apresentando a mutação T369G no genoma. As 13 pacientes restantes foram positivas para a variante HPV6vc, não apresentando alterações nucleotídicas. Na análise das amostras HPV11, observou-se que todas as pacientes mostraram as mutações T137C e C380T. Além disso, uma paciente também apresentou a alteração nucleotídica T410C. Nenhuma das alterações nucleotídicas encontradas apresentou troca de aminoácido. Na análise estatística, foi possível observar uma associação significante entre a coinfecção de HPV com HIV e também foi observada uma associação significante entre a infecção por HPV11 e o consumo de bebida alcoólica. Os demais dados analisados não mostraram associação significante. Na análise filogenética foi possível observar o agrupamento das amostras de acordo com suas variantes, não mostrando relação com a região geográfica as quais foram isoladas. Condyloma acuminatum (CA) or genital warts are benign proliferative lesions that can be epidermal or mucous. Condyloma is caused by infection with human papillomavirus (HPV), mainly the low-risk types 6 and 11, but can also occur coinfection with high-risk HPVs. Human papillomaviruses have the capacity to infect the skin, oral and genital mucosa, and induce benign or malignant proliferative lesions. The variants of HPVs are defined as viral sequences that share identity in the nucleotide sequence of the L1 gene greater than 98%. Based on this criterion, HPV6 and 11 variants lineages have been studied and there is still an attempt to correlate these genetic variants with different clinical findings of infection. In this way, the aim of this study was to detect variants and nucleotide alterations presents in E6 region of HPV types 6 and 11 detected in condyloma acuminatum samples, to correlate the HPV presence with the clinical-pathological data of the patients and to determine phylogenetic relations of variants found with variants of others places of the world. The E6 region of 32 samples of condyloma were sequenced, being 25 positive to HPV6 and seven diagnosed HPV11. Twelve samples were identified as the HPV6a variant, and presented the mutation G474A, and one of these also showed the mutation T369G. The others 13 patients were positive to HPV6vc without nucleotide alterations. In the analysis of the seven HPV11 samples, it was observed that all patients showed the mutations T137C and C380T. Besides that, one patient also present the nucleotide alteration T410C. None of the mutations showed amino acid change. In the statistical analysis, it was observed a significant association between the HPV and HIV coinfection, and it was also found a significant association between HPV11 and alcohol consumption. Others data analyzed did not show significant association. In the phylogenetic analysis, it was observed that the samples were grouped according to variants, showing no relation to the geographical region that they were isolated. FAPESP: 2015/06628-7

Background. Recurrent respiratory papillomatosis (RRP) is mainly associated with human papillomavirus (HPV) 6 or HPV11. The purpose of this study was to compare clinical outcome, aggressiveness, and treatment response between HPV6- and HPV11-associated RRP. Methods. A retrospective cohort of 55 patients with RRP (1974-2012) was used. Surgical interventions (n = 814) were analyzed, and complications scored. HPV6/11-specific polymerase chain reaction (PCR) was performed on RRP biopsies. Results. Seventy-six percent of patients (42 of 55) were infected with HPV6 and 24% (13 of 55) with HPV11. The HPV11 group had anatomically more widespread disease. The expected number of surgical interventions was higher in the younger age ( Conclusion. Anatomically, HPV11-associated RRP behaves more aggressively. Younger patients with HPV11 and older patients with HPV6 experience a worse clinical course of RRP. (C) 2014 Wiley Periodicals, Inc.

Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution. Fil: Jelen, Mateja M. University of Ljubljana; Eslovenia Fil: Chen, Zigui. Albert Einstein College of Medicine. New York; Estados Unidos Fil: Kocjan, Botjan J.. University of Ljubljana; Eslovenia Fil: Burt, Felicity J.. University of the Free State. Bloemfontein; Sudáfrica Fil: Chan, Paul K.S.. Chinese University of Hong Kong; China Fil: Chouhy, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Combrinck, Catharina E.. University of the Free State. Bloemfontein; Sudáfrica Fil: Coutlee, Francois. Hôpital Notre-Dame-Pavillon Deschamps. Montréal; Canadá Fil: Estrade, Christine. Lausanne University Hospital; Suiza Fil: Ferenczy, Alex. McGill University and Jewish General Hospital. Montreal; Canadá Fil: Fiander, Alison. Institute of Cancer and Genetics. Cardiff; Reino Unido Fil: Franco, Eduardo L.. McGill University. Montreal; Canadá Fil: Garland, Suzanne M.. The Royal Women's Hospital. Parkville; Australia. The University of Melbourne; Australia. Murdoch Children's Research Institute. Victoria; Australia Fil: Giri, Adriana Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: González, Joaquín Víctor. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud; Argentina Fil: Gröning, Arndt. Medizinisches Versorgungszentrum wagnerstibbe für Laboratoriumsmedizin und Pathologie GmbH. Hannover; Alemania Fil: Heidrich, Kerstin. Medizinisches Versorgungszentrum wagnerstibbe für Laboratoriumsmedizin und Pathologie GmbH. Hannover; Alemania Fil: Hibbitts, Sam. Institute of Cancer and Genetics. Cardiff; Reino Unido Fil: Hosnjak, Lea. University of Ljubljana; Eslovenia Fil: Luk, Tommy N.M. The Chinese University of Hong Kong; China. Hong Kong Special Administrative Region; China Fil: Marinic, Karina. Hospital Dr. Julio C. Perrando. Chaco; Argentina Fil: Matsukura, Toshihiko. National Institute of Health. Tokyo; Japón Fil: Neumann, Anna. The University of Melbourne; Australia. Medizinisches Versorgungszentrum wagnerstibbe für Laboratoriumsmedizin und Pathologie GmbH. Hannover; Alemania Fil: Oštrbenk, Anja. University of Ljubljana; Eslovenia Fil: Picconi, Maria Alejandra. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud; Argentina Fil: Richardson, Harriet. Queen's University. Ontario; Canadá Fil: Sagadin, Martin. University of Ljubljana; Eslovenia Fil: Sahli, Roland. Lausanne University Hospital; Suiza Fil: Seedat, Riaz Y.. University of the Free State. Bloemfontein; Sudáfrica Fil: Seme, Katja. University of Ljubljana; Eslovenia Fil: Severini, Alberto. Public Health Agency of Canada. Winnipeg; Canadá Fil: Sinchi, Jessica L. Hospital Dr. Julio C. Perrando. Chaco; Argentina Fil: Smahelova, Jana. Institute of Hematology and Blood Transfusion. Praga; República Checa Fil: Tabrizi, Sepehr N.. The University of Melbourne; Australia. Murdoch Children's Research Institute. Victoria; Australia. The Royal Women's Hospital. Parkville; Australia Fil: Tachezy, Ruth. Institute of Hematology and Blood Transfusion. Praga; República Checa Fil: Tohme, Sarah. Public Health Agency of Canada. Winnipeg; Canadá Fil: Uloza, Virgilijus. Lithuanian University of Health Sciences. Kaunas; Lituania Fil: Vitkauskiene, Astra. Lithuanian University of Health Sciences. Kaunas; Lituania Fil: Wong, Yong Wee. Universti Kebangsaan Malaysia. Bangi; Malasia Fil: Lepeja, Snježana Židovec. University Hospital for Infectious Diseases Dr. Fran Mihaljević. Zagreb; Croacia Fil: Burk, Robert D.. Albert Einstein College of Medicine.New York; Estados Unidos Fil: Poljak, Mario. Albert Einstein College of Medicine. New York; Estados Unidos

A key effect of human papillomavirus (HPV) infection is to disrupt the normal cell cycle in order to subvert the cellular DNA replication machinery. Morphologically, condylomata induced by high and low risk HPV types cannot be distinguished and many studies have shown that the pattern of viral gene expression is similar in condylomata caused by both high risk and low risk HPV types. Detailed morphological study of cell cycle protein expression has not previously been performed on condylomata infected with low risk HPV types. The findings presented suggest that the mechanisms employed by low risk HPV6 or HPV11 to subvert cellular functions in condylomata acuminata are similar to those employed by high risk HPVs, with the exception of cyclin D1 and p53 protein over-expression. The differences in p53 expression and cyclin D1 expression seen between high and low risk HPV infection, reflect the known differences between high and low risk types and are in agreement with the known differences between high risk and low risk E6 and E7 proteins. PHK transduction studies demonstrated HPV E6 and E7 induce changes in cell cycle protein expression and that there are differences in cell cycle abrogation between HPV6 and HPV16. Disruption of the p53-MDM2 interaction can lead to activation of the p53 pathway. HPV infected lesions almost always contain wild-type p53. The binding of HPV E6 to p53, and its subsequent targeting for degradation, prevents activation of the p53 pathway in HPV infected cells. Cells over expressing HPV genes were treated with Nutlin-3, a MDM2-small molecule antagonist. The findings presented suggest treatment with Nutlin-3 induces cell cycle arrest in cells expressing HPV16 E7 and HPV6 E6 and HPV6 E7. This suggests a potential role for Nutlin-3 in the treatment of HPV infected cells.