RESUMEN
OBJECTIVES: To determine the prevalence, viral load, tissue tropism, and genetic variability of novel human papillomavirus (HPV) type 179, which is etiologically associated with sporadic cases of common warts in immunocompromised patients, and phylogenetically related HPV types 135 and 146. METHODS: The representative collection of 850 HPV-associated clinical samples (oral/nasopharyngeal/anal, archival specimens of oral/oropharyngeal/conjunctival/cervical/skin cancer, benign lesions of the larynx/conjunctiva/skin, and eyebrows), obtained from immunocompetent individuals, was tested for the presence of HPV179, HPV135, and HPV146 using type-specific real-time PCRs. To assess the genetic diversity of the HPVs investigated in the non-coding long control region (LCR), several highly sensitive nested PCR protocols were developed for each HPV type. The genetic diversity of HPV179 was additionally determined in 12 HPV179 isolates from different anatomical sites of an only immunocompromised patient included in the study. RESULTS: HPV179, HPV135, and HPV146 were detected in 1.4, 2.0, and 1.5% of the samples tested, respectively, with no preference for cutaneous or mucosal epithelial cells. One (with five single nucleotide polymorphisms; SNPs), four (with one to six SNPs), and four (with one to eight SNPs) genetic variants of HPV179, HPV135, and HPV146, respectively, were identified among eligible samples. HPV179 isolates from the immunocompromised patient exhibited the identical LCR nucleotide sequence, suggesting that HPV179 can cause generalized HPV infections. CONCLUSIONS: HPV179, HPV135, and HPV146 have a mucocutaneous tissue tropism and are associated with sporadic infections in immunocompromised and immunocompetent individuals. Because the majority of mutations were found outside the major functional domains of the respective LCRs, we assume that HPV179, HPV135, and HPV146 genetic variants pathogenically do not differ from their prototypes. In addition, no association was found between specific HPV179, HPV135, and HPV146 genetic variants and anatomical sites of infection and/or specific neoplasms.
Asunto(s)
Gammapapillomavirus/genética , Variación Genética , Gammapapillomavirus/fisiología , Humanos , Carga ViralRESUMEN
Data regarding the anogenital distribution of and type-specific concordance for cutaneous ß- and γ-HPV types in men who have sex with women is limited and geographically narrow. Knowledge of determinants of anogenital detection of cutaneous HPV types in different regions is needed for better understanding of the natural history and transmission dynamics of HPV, and its potential role in the development of anogenital diseases. Genital and anal canal samples obtained from 554 Russian men were screened for 43 ß-HPVs and 29 γ-HPVs, using a multiplex PCR combined with Luminex technology. Both ß- and γ-HPVs were more prevalent in the anal (22.8% and 14.1%) samples than in the genital (16.8% and 12.3%) samples. Low overall and type-specific concordance for ß-HPVs (3.5% and 1.1%) and γ-HPVs (1.3% and 0.6%) were observed between genital and anal samples. HIV-positive men had higher anal ß- (crude OR = 12.2, 95% CI: 5.3-28.1) and γ-HPV (crude OR = 7.2, 95% CI: 3.3-15.4) prevalence than HIV-negative men. Due to the lack of genital samples from the HIV-positive men, no comparison was possible for HIV status in genital samples. The lack of type-specific positive concordance between genital and anal sites for cutaneous ß- and γ-HPV types in heterosexual men posits the needs for further studies on transmission routes to discriminate between contamination and true HPV infection. HIV-positive status may favor the anal acquisition or modify the natural history of cutaneous HPV types.
Asunto(s)
Canal Anal/virología , Betapapillomavirus/fisiología , Gammapapillomavirus/fisiología , Genitales Masculinos/virología , Infecciones por VIH/epidemiología , VIH-1/fisiología , Infecciones por Papillomavirus/epidemiología , Adolescente , Adulto , Coinfección , Genotipo , Heterosexualidad , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Federación de Rusia/epidemiología , Adulto JovenAsunto(s)
Alphapapillomavirus/fisiología , Gammapapillomavirus/fisiología , Infecciones por Papillomavirus/virología , Neoplasias Cutáneas/virología , Adulto , Alphapapillomavirus/genética , Alphapapillomavirus/aislamiento & purificación , Alphapapillomavirus/patogenicidad , Aminoquinolinas/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virología , Niño , Terapia Combinada , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/terapia , Condiloma Acuminado/virología , Criocirugía , Crioterapia , Femenino , Gammapapillomavirus/genética , Gammapapillomavirus/aislamiento & purificación , Gammapapillomavirus/patogenicidad , Humanos , Imiquimod , Huésped Inmunocomprometido , Terapia por Láser , Láseres de Gas , Masculino , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/fisiopatología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/terapia , Vacunas contra Papillomavirus , Podofilotoxina/uso terapéutico , Embarazo , Complicaciones Neoplásicas del Embarazo/cirugía , Complicaciones Neoplásicas del Embarazo/virología , Riesgo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/virología , Vacunación , Verrugas/tratamiento farmacológico , Verrugas/cirugía , Verrugas/virología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/terapia , Displasia del Cuello del Útero/virologíaRESUMEN
RNAi (RNA interference) is a natural process by which eukaryotic cells silence gene expression through small interference RNAs (siRNA) which are complementary to messenger RNA (mRNA). In this process, the siRNA that are 21-25 nucleotides long and are known as microRNA (miRNA), either associate with the RNA-induced silencing complex (RISC), which targets and cleaves the complementary mRNAs by the endonucleolytic pathway, or repress the translation. It is also possible to silence exogenous gene expression during viral infections by using DNA templates to transcribe siRNA with properties that are identical to those of bioactive microRNA. Persistent human papillomavirus (HPV) infection is the main etiological agent during cervical cancer development and the HPV E6 and E7 oncogenes, which induce cellular transformation and immortalization, represent strategic targets to be silenced with siRNA. In several in vitro and in vivo studies, it has been demonstrated that the introduction of siRNA directed against the E6 and E7 oncogenes in human tumoral cervical cells transformed by HPV, leads to the efficient silencing of HPV E6 and E7 oncogene expression, which induces the accumulation of the products of the p53 and pRb tumor suppressor genes and activates the mechanism of programmed cell death by apoptosis; thus, the progression of the tumoral growth process may be prevented. The goal of this review is to analyze the microRNA biogenesis process in the silencing of gene expression and to discuss the different protocols for the use of siRNA as a potential gene therapy strategy for the treatment of cervical cancer.