RESUMEN
BACKGROUND: Papilloma DNA viruses are one of the viruses that cause skin lesions in ruminants. OBJECTIVES: The clinical, histopathological and molecular characteristics of cutaneous papilloma in ruminants in Iran are to be investigated in this study. METHODS: Samples were collected from 19 small ruminants (5 sheep and 14 goats) with various papillomatosis lesions. The samples taken were studied with histopathological and molecular techniques. RESULTS: In clinical terms, the lesions appeared in different sizes, ranging from 0.5 to 11 cm, and the cauliflower exophytic masses appeared in other parts of the animal's body. In the limbs, most papilloma lesions have been seen (42.1%). In histopathological examination, perinuclear vacuolation epidermal granule layer with various degrees of hypergranulosis, hyperkeratosis, acanthosis, orthokeratosis and parakeratosis were seen. Moreover, all the suspected samples were positive for papillomavirus using the polymerase chain reaction technique. CONCLUSIONS: Although the prevalence of papillomaviruses in Iranian sheep and goats is low, it seems necessary to distinguish them from other viral skin diseases, such as cutaneous contagious ecthyma, using molecular techniques and histopathology.
Asunto(s)
Enfermedades de las Cabras , Cabras , Papillomaviridae , Infecciones por Papillomavirus , Enfermedades de las Ovejas , Animales , Irán/epidemiología , Enfermedades de las Ovejas/virología , Enfermedades de las Ovejas/epidemiología , Enfermedades de las Ovejas/patología , Ovinos , Enfermedades de las Cabras/virología , Enfermedades de las Cabras/patología , Enfermedades de las Cabras/epidemiología , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , Infecciones por Papillomavirus/veterinaria , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/epidemiología , Papiloma/veterinaria , Papiloma/virología , Papiloma/patología , Papiloma/epidemiología , Reacción en Cadena de la Polimerasa/veterinaria , Femenino , Prevalencia , Masculino , Oveja DomésticaRESUMEN
Laryngopharynx epithelium neoplasia induced by HPV6/11 infection in juvenile-onset recurrent respiratory papillomatosis (JO-RRP) causes a great health issue characteristic of frequent relapse and aggressive disease progression. Local cell-mediated immunity shaped by the recruitment and activation of cytotoxic effector cells is critical for viral clearance. In this study, we found that NK cells in the papillomas of aggressive JO-RRP patients, in contrast to massive infiltrated T cells, were scarce in number and impaired in activation and cytotoxicity as they were in peripheral blood. Data from cell infiltration analysis indicated that the migration of NK cell to papilloma was restricted in aggressive JO-RRP patients. Further study showed that the skewed chemokine expression in the papillomas and elevated ICAM-1 expression in hyperplastic epithelia cells favored the T cell but not NK cell recruitment in aggressive JO-RRP patients. In parallel to the increased CD3+ T cells, we observed a dramatical increase in Tregs and Treg-promoting cytokines such as IL-4, IL-10 and TGFß in papillomas of aggressive JO-RRP patients. Our study suggested that likely initialized by the intrinsic change in neoplastic epithelial cells with persistent HPV infection, the aggressive papillomas built an entry barrier for NK cell infiltration and formed an immunosuppressive clump to fend off the immune attack from intra-papillomas NK cells. IMPORTANCE Frequent relapse and aggressive disease progression of juvenile-onset recurrent respiratory papillomatosis (JO-RRP) pose a great challenge to the complete remission of HPV 6/11 related laryngeal neoplasia. Local immune responses in papillomas are more relevant to the disease control considering the locale infected restriction of HPV virus in epitheliums. In our study, the restricted NK cell number and reduced expression of activating NKp30 receptor suggested one possible mechanism underlying impaired NK cell defense ability in aggressive JO-RRP papillomas. Meanwhile, the negative impact of HPV persistent infection on NK cell number and function represented yet another example of a chronic pathogen subverting NK cell behavior, affirming a potentially important role for NK cells in viral containment. Further, the skewed chemokine/cytokine expression in the papillomas and the elevated adhesion molecules expression in hyperplastic epithelia cells provided important clues for understanding blocked infiltration and antiviral dysfunction of NK cells in papilloma.
Asunto(s)
Células Asesinas Naturales , Papiloma , Infecciones por Papillomavirus , Infecciones del Sistema Respiratorio , Progresión de la Enfermedad , Papillomavirus Humano 11 , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-10/inmunología , Interleucina-4/inmunología , Células Asesinas Naturales/inmunología , Receptor 3 Gatillante de la Citotoxidad Natural/metabolismo , Recurrencia Local de Neoplasia , Papiloma/inmunología , Papiloma/virología , Infecciones por Papillomavirus/inmunología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/virología , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
Laryngeal papilloma (LP), which is associated with infection by human papillomavirus (HPV)-6 or -11, displays aggressive growth. The precise molecular mechanism underlying the tumorigenesis of LP has yet to be uncovered. Building on our earlier research into HPV-6, in this study, the viral gene expression of HPV-11 was investigated by quantitative PCR and DNA/RNA in situ hybridization. Additionally, newly developed antibodies against the E4 protein of HPV-6 and HPV-11 were evaluated by immunohistochemistry. The average viral load of HPV-11 in LP was 1.95 ± 0.66 × 105 copies/ng DNA, and 88% of HPV mRNA expression was found to be E4, E5a, and E5b mRNAs. According to RNA in situ hybridization, E4 and E5b mRNAs were expressed from the middle to upper part of the epithelium. E4 immunohistochemistry revealed a wide positive reaction in the upper cell layer in line with E4 mRNA expression. Other head and neck lesions with HPV-11 infection also showed a positive reaction in E4 immunohistochemistry. The distribution pattern of HPV DNA, viral mRNA, and E4 protein in LP with HPV-11 infection was quite similar to that of HPV-6. Therefore, it might be possible to apply these E4-specific antibodies in other functional studies as well as clinical applications, including targeted molecular therapies in patients with HPV-6 and HPV-11 infection.
Asunto(s)
Anticuerpos Antivirales , Papillomavirus Humano 11 , Papillomavirus Humano 6 , Neoplasias Laríngeas/inmunología , Papiloma/inmunología , ADN Viral , Papillomavirus Humano 11/fisiología , Papillomavirus Humano 6/fisiología , Humanos , Inmunohistoquímica , Hibridación in Situ , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/virología , Papiloma/patología , Papiloma/virología , Infecciones por Papillomavirus/inmunología , ARN Mensajero/metabolismo , Carga ViralRESUMEN
MmuPV1 is a useful model for studying papillomavirus-induced tumorigenesis. We used RNA-seq to look for chimeric RNAs that map to both MmuPV1 and host genomes. In tumor tissues, a higher proportion of total viral reads were virus-host chimeric junction reads (CJRs) (1.9 - 7) than in tumor-free tissues (0.6 - 1.3): most CJRs mapped to the viral E2/E4 region. Although most of the MmuPV1 integration sites were mapped to intergenic regions and introns throughout the mouse genome, integrations were seen more than once in several genes: Malat1, Krt1, Krt10, Fabp5, Pard3, and Grip1; these data were confirmed by rapid amplification of cDNA ends (RACE)-Single Molecule Real-Time (SMRT)-seq or targeted DNA-seq. Microhomology sequences were frequently seen at host-virus DNA junctions. MmuPV1 infection and integration affected the expression of host genes. We found that factors for DNA double-stranded break repair and microhomology-mediated end-joining (MMEJ), such as H2ax, Fen1, DNA polymerase Polθ, Cdk1, and Plk1, exhibited a step-wise increase and Mdc1 a decrease in expression in MmuPV1-infected tissues and MmuPV1 tumors relative to normal tissues. Increased expression of mitotic kinases CDK1 and PLK1 appears to be correlated with CtIP phosphorylation in MmuPV1 tumors, suggesting a role for MMEJ-mediated DNA joining in the MmuPV1 integration events that are associated with MmuPV1-induced progression of tumors.
Asunto(s)
Reparación del ADN por Unión de Extremidades , Enzimas Reparadoras del ADN/metabolismo , ADN Viral/genética , Queratinocitos/metabolismo , Papiloma/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/genética , Animales , Animales Recién Nacidos , Roturas del ADN de Doble Cadena , Enzimas Reparadoras del ADN/genética , Femenino , Genoma Viral , Recombinación Homóloga , Queratinocitos/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Papiloma/virología , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/virología , RNA-SeqRESUMEN
We study a patient with the human papilloma virus (HPV)-2-driven "tree-man" phenotype and two relatives with unusually severe HPV4-driven warts. The giant horns form an HPV-2-driven multifocal benign epithelial tumor overexpressing viral oncogenes in the epidermis basal layer. The patients are unexpectedly homozygous for a private CD28 variant. They have no detectable CD28 on their T cells, with the exception of a small contingent of revertant memory CD4+ T cells. T cell development is barely affected, and T cells respond to CD3 and CD2, but not CD28, costimulation. Although the patients do not display HPV-2- and HPV-4-reactive CD4+ T cells in vitro, they make antibodies specific for both viruses in vivo. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1. The control of HPV-2 and HPV-4 in keratinocytes is dependent on the T cell CD28 co-activation pathway. Surprisingly, human CD28-dependent T cell responses are largely redundant for protective immunity.
Asunto(s)
Antígenos CD28/deficiencia , Patrón de Herencia/genética , Papillomaviridae/fisiología , Piel/virología , Linfocitos T/inmunología , Adulto , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Antígenos CD28/genética , Antígenos CD28/metabolismo , Linfocitos T CD4-Positivos/inmunología , Niño , Endopeptidasas/metabolismo , Femenino , Genes Recesivos , Células HEK293 , Homocigoto , Humanos , Inmunidad Humoral , Memoria Inmunológica , Células Jurkat , Queratinocitos/patología , Masculino , Ratones Endogámicos C57BL , Oncogenes , Papiloma/patología , Papiloma/virología , Linaje , Señales de Clasificación de Proteína , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Interaction of the long control region (LCR) and the E2 protein of HPV11s was studied by in silico modelling and in vitro functional analysis. Genomes of HPV11s from fifteen (six known and nine novel) patients (two solitary papillomas, eleven respiratory papillomatoses of different severity, one condyloma acuminatum and one cervical atypia) were sequenced; E2 polymorphisms were analysed in silico by protein modelling. E2 and LCR variants were cloned into pcDNA3.1+ expression vector and into pALuc reporter vector, respectively, transfected to HEp2 cells alone or in different combinations and the luciferase activity was measured. In the E2, the ubiquitous polymorphism K308R caused stronger binding between the dimers but did not alter DNA binding; E2s with this polymorphism were significantly less efficient than the reference in promoting LCR activity. The unique polymorphism Q86K changed the negative surface charge of E2 (Q86) to positive (K86). The unique polymorphisms S245F and N247T in the hinge region disrupt a probable phosphorylation site in a RXXS motif targeted by protein kinase A and B, but do not affect directly the amino acids critical to nuclear transport. Both unique patterns partly restored the LCR activating potential disrupted by K308R. A unique E2/E4 ORF with a 58-bp deletion leading to a frameshift and an early stop codon resulted in a practically nonfunctional E2, and was associated with a papillomatosis with dysplasia. When testing existing LCR-E2 combinations, LCR with intrinsically lower enhancer capacity was only marginally activated by its E2 (R308 and the deletion mutant), and did not significantly exceed the activity of the reference LCR without E2. Combined with more potent LCRs associated with more severe disease, the activity was significantly higher, but still significantly lower than LCRs with reference E2. In summary, LCR-E2 interaction determined by their polymorphisms may explain, at least partly, differences in disease severity.
Asunto(s)
Papillomavirus Humano 11/genética , Papiloma/virología , Infecciones por Papillomavirus/virología , Polimorfismo Genético , Proteínas Virales/genética , Condiloma Acuminado/virología , Femenino , Humanos , Masculino , Infecciones del Sistema Respiratorio/virología , Índice de Severidad de la EnfermedadAsunto(s)
Alphapapillomavirus/aislamiento & purificación , Trasplante de Médula Ósea/efectos adversos , Papiloma/terapia , Infecciones por Papillomavirus/terapia , Vacunas contra Papillomavirus/uso terapéutico , Neoplasias de la Lengua/terapia , Enfermedad Injerto contra Huésped/etiología , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Papiloma/virología , Infecciones por Papillomavirus/virología , Recurrencia , Inducción de Remisión , Neoplasias de la Lengua/virología , Vacunación , Carga ViralRESUMEN
Pathogen-induced cancers account for 15% of human tumors and are a growing concern for endangered wildlife. Fibropapillomatosis is an expanding virally and environmentally co-induced sea turtle tumor epizootic. Chelonid herpesvirus 5 (ChHV5) is implicated as a causative virus, but its transmission method and specific role in oncogenesis and progression is unclear. We applied environmental (e)DNA-based viral monitoring to assess viral shedding as a direct means of transmission, and the relationship between tumor burden, surgical resection and ChHV5 shedding. To elucidate the abundance and transcriptional status of ChHV5 across early, established, regrowth and internal tumors we conducted genomics and transcriptomics. We determined that ChHV5 is shed into the water column, representing a likely transmission route, and revealed novel temporal shedding dynamics and tumor burden correlations. ChHV5 was more abundant in the water column than in marine leeches. We also revealed that ChHV5 is latent in fibropapillomatosis, including early stage, regrowth and internal tumors; higher viral transcription is not indicative of poor patient outcome, and high ChHV5 loads predominantly arise from latent virus. These results expand our knowledge of the cellular and shedding dynamics of ChHV5 and can provide insights into temporal transmission dynamics and viral oncogenesis not readily investigable in tumors of terrestrial species.
Asunto(s)
ADN Ambiental/análisis , Herpesviridae/genética , Tortugas/virología , Verrugas/transmisión , Animales , Carcinogénesis/genética , ADN/genética , Monitoreo del Ambiente/métodos , Genómica/métodos , Herpesviridae/patogenicidad , Sanguijuelas/genética , Sanguijuelas/patogenicidad , Papiloma/etiología , Papiloma/virología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/virología , Tortugas/genética , Esparcimiento de Virus/genética , Verrugas/veterinaria , Verrugas/virologíaAsunto(s)
Enfermedad Crónica/terapia , Papiloma/diagnóstico , Papiloma/terapia , Papiloma/virología , Enfermedades de la Tráquea/diagnóstico , Enfermedades de la Tráquea/terapia , Enfermedades de la Tráquea/virología , Tos/diagnóstico , Tos/terapia , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Numerous raised plaques were observed on the feet of a red-billed gull (Chroicocephalus novaehollandiae scopulinus) that had been found dead. The plaques consisted of thickened epidermis with cell changes indicative of papillomavirus (PV) infection prominent within affected areas. Evidence suggesting progression to neoplasia was visible in one lesion. A DNA sequence that was most similar, but only 68.3% identical, to duck PV type 3 was amplified from the papillomas, suggesting a novel PV type. Lesions containing PV DNA have only previously been reported in three avian species. This is the first evidence that PVs could cause neoplasia in birds.
Asunto(s)
Enfermedades de las Aves/virología , Carcinoma in Situ/veterinaria , Charadriiformes/virología , Papiloma/veterinaria , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/veterinaria , Animales , Enfermedades de las Aves/patología , Proteínas de la Cápside/genética , Carcinoma in Situ/patología , Carcinoma in Situ/virología , ADN Viral/genética , Pie/patología , Pie/virología , Papiloma/patología , Papiloma/virología , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , FilogeniaRESUMEN
Human papillomavirus (HPV) types 6 and 11 are the etiological agents of recurrent respiratory papillomatosis (RRP). We examined the prevalence and distribution of HPVs 6 and 11 genetic variants in juvenile onset (JORRP) and adult onset (AORRP) laryngeal papillomas. Cases of JORRP and AORRP were collected, retrospectively. HPV detection and genotyping were accessed by polymerase chain reaction-sequencing in 67 RRP samples. Overall, the most prevalent HPV-6 variants were from B1 (55.8%) and B3 (27.9%) sublineages, whereas among HPV-11 positive samples A2 (62.5%) variants were predominant. A higher prevalence of HPV-6 B1 was observed in JORRP (83.3% B1 and 16.7% B3), compared with AORRP cases (58.3% B1 and 41.7% B3). HPV-11 A2 variants were more prevalent both in JORRP (57.2%) and in AORRP cases (70.0%). Nevertheless, with the exception that HPV-6 B1 were significantly less likely to recur, there was a lack of association between any particular HPVs 6 or 11 variant and clinicopathological features. Our data do not support an association between HPVs 6 and 11 variability and RRP.
Asunto(s)
Variación Genética , Papillomavirus Humano 11/genética , Papillomavirus Humano 6/genética , Neoplasias Laríngeas/virología , Papiloma/virología , Infecciones por Papillomavirus/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Adolescente , Adulto , Femenino , Genotipo , Humanos , Masculino , Infecciones por Papillomavirus/virología , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
Papillomavirus (PV) infections are associated with the development of cutaneous and mucosal tumors in humans and various animal species. In humans, infection of high-risk human PVs (HPVs) causes anogenital cancers, while in animals, anogenital-associated PVs are not well understood. Among animal PVs, Bos taurus PVs (BPVs) have the most diverse genotypes, up to 28 of them. The present study will report two unique BPVs identified in vulval papilloma lesions from two Holstein Friesian cattle by conventional PCR and sequencing. In the first case, BPV28 harboring two L1 open reading frames (ORFs) due to a five-nucleotide deletion was identified. In the second case, histologically diagnosed as papilloma, an unclassified BPV genotype was detected. However, in both cases, the immunohistochemistry against PV antigen was negative. The full genome of the unclassified BPV was amplified by inverse PCR and analyzed by genome-walking sequencing. The L1 nucleotide sequence was most identical to BPV genotype 6 (BPV6), showing 78 % identity, indicating that this novel BPV should be classified as species Xipapillomavirus 1, genotype BPV29. The mRNA expression of three early genes (E1, E2, E10), but not L1, was confirmed in both BPV28- and BPV29-detected papilloma lesions. The present study suggests the involvement of novel types of BPV in vulval papilloma. The alteration of BPV28 pathogenicity due to the frameshift mutation of L1 needs to be elucidated in the future.
Asunto(s)
Papiloma/veterinaria , Infecciones por Papillomavirus/veterinaria , Vulva/microbiología , Vulva/patología , Xipapillomavirus/genética , Animales , Bovinos , Femenino , Mutación del Sistema de Lectura , Genoma Viral , Genotipo , Japón , Papiloma/virología , Infecciones por Papillomavirus/virología , Xipapillomavirus/clasificación , Xipapillomavirus/patogenicidadRESUMEN
Papillomaviruses (PVs) are an extremely large group of viruses that cause skin and mucosa infections in humans and various animals. In roe deer and red deer, most PVs belong to the Deltapapillomavirus genus and cause neoplastic changes that are generally described as fibropapillomas. Despite the wide distribution of roe and red deer throughout Europe and beyond, the data in the scientific literature regarding the widespread distribution of PVs and the genetic variability of PV genomes in these species are rather scarce. This study describes cutaneous fibropapillomatosis cases in roe and red deer with clinical manifestations that are typical of infections with PVs. In all cases, the presence of PV DNA was confirmed using PCR, followed by Sanger sequencing of the partial L1 gene. The complete PV genomes were determined in all the investigated samples using next-generation sequencing technology, revealing infections of roe deer with the CcaPV1-type and red deer with the CePV1v-type variant. A comparison of the complete CcaPV1-type and CePV1v-type variant genome sequences reported here with already available complete genome sequences in GenBank revealed their great genetic stability across time and space.
Asunto(s)
Ciervos/virología , Deltapapillomavirus/genética , Genoma Viral , Papiloma/veterinaria , Infecciones por Papillomavirus/veterinaria , Animales , Deltapapillomavirus/clasificación , Deltapapillomavirus/aislamiento & purificación , Papiloma/virología , Infecciones por Papillomavirus/virología , Filogenia , Proteínas Virales/genética , Secuenciación Completa del GenomaRESUMEN
CONTEXT: The coronavirus disease 2019 (COVID-19) pandemic raised concerns about the safety of laparoscopy due to the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diffusion in surgical smoke. Although no case of SARS-CoV-2 contagion related to surgical smoke has been reported, several international surgical societies recommended caution or even discouraged the use of a laparoscopic approach. OBJECTIVE: To evaluate the risk of virus spread due to surgical smoke during surgical procedures. EVIDENCE ACQUISITION: We searched PubMed and Scopus for eligible studies, including clinical and preclinical studies assessing the presence of any virus in the surgical smoke from any surgical procedure or experimental model. EVIDENCE SYNTHESIS: We identified 24 studies. No study was found investigating SARS-CoV-2 or any other coronavirus. About other viruses, hepatitis B virus was identified in the surgical smoke collected during different laparoscopic surgeries (colorectal resections, gastrectomies, and hepatic wedge resections). Other clinical studies suggested a consistent risk of transmission for human papillomavirus (HPV) in the surgical treatments of HPV-related disease (mainly genital warts, laryngeal papillomas, or cutaneous lesions). Preclinical studies showed conflicting results, but HPV was shown to have a high risk of transmission. CONCLUSIONS: Although all the available data come from different viruses, considering that the SARS-CoV-2 virus has been shown in blood and stools, the theoretical risk of virus diffusion through surgical smoke cannot be excluded. Specific clinical studies are needed to understand the effective presence of the virus in the surgical smoke of different surgical procedures and its concentration. Meanwhile, adoption of all the required protective strategies, including preoperative patient nasopharyngeal swab for COVID-19, seems mandatory. PATIENT SUMMARY: In this systematic review, we looked at the risk of virus spread from surgical smoke exposure during surgery. Although no study was found investigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or any other coronavirus, we found that the theoretical risk of virus diffusion through surgical smoke cannot be excluded.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/transmisión , Virus de la Hepatitis B , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Laparoscopía , Papillomaviridae , Neumonía Viral/transmisión , Humo , COVID-19 , Colectomía , Condiloma Acuminado/cirugía , Condiloma Acuminado/virología , Gastrectomía , Hepatectomía , Humanos , Neoplasias Laríngeas/cirugía , Neoplasias Laríngeas/virología , Procedimientos Quirúrgicos Mínimamente Invasivos , Pandemias , Papiloma/cirugía , Papiloma/virología , Infecciones por Papillomavirus , Riesgo , SARS-CoV-2 , Verrugas/cirugía , Verrugas/virologíaRESUMEN
SARS-CoV-2 is assumed to use angiotensin-converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and there has been speculation that SARS-CoV-2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctivas, 12 melanomas, seven squamous cell carcinomas, and seven papilloma samples, were analyzed using high-throughput RNA sequencing to assess messenger RNA (mRNA) expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS-CoV-2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median: 0.0 transcripts per million [TPM], min: 0.0 TPM, max: 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS-CoV-2 via these mediators unlikely.
Asunto(s)
COVID-19/virología , Carcinoma de Células Escamosas/virología , Neoplasias del Ojo/virología , Melanoma/virología , Papiloma/virología , Receptores Virales/genética , Adulto , Anciano , Anciano de 80 o más Años , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/complicaciones , COVID-19/patología , COVID-19/cirugía , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Estudios de Casos y Controles , Conjuntiva/patología , Conjuntiva/cirugía , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Neoplasias del Ojo/complicaciones , Neoplasias del Ojo/patología , Neoplasias del Ojo/cirugía , Expresión Génica , Glutamil Aminopeptidasa/genética , Glutamil Aminopeptidasa/metabolismo , Humanos , Inmunohistoquímica , Masculino , Melanoma/complicaciones , Melanoma/patología , Melanoma/cirugía , Persona de Mediana Edad , Papiloma/complicaciones , Papiloma/patología , Papiloma/cirugía , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Virales/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismoRESUMEN
Sinonasal papillomas are rare, usually benign tumors arising from the Schneiderian membrane. Human papillomaviruses (HPV) can infect differentiating skin and mucosal cells and can induce uncontrolled growth patterns. Their effect on development of sinonasal papillomas has been discussed controversially in recent years. A monocentric, retrospective study was conducted to investigate histopathologic features of sinonasal papillomas and to establish an assay for HPV detection and genotyping in papillomas. Schneiderian papillomas are divided into three groups according to histopathologic features: the largest group are inverted papillomas, followed by fungiform (exophytic) and oncocytic papillomas. HPV screening was performed with high sensitivity by PCR employing My09/11 and 125 consensus primers. Adding a third primer pair (GP5+/GP6+) d increase sensitivity. Reverse hybridization microarrays achieved HPV genotyping better than pyrosequencing in our setting. HPV infection rates were higher in papillomas (46.7%) than infection rates reported for healthy mucosa (up to 13%). P16(INK4a) was not a reliable surrogate marker for HPV infection in sinonasal papillomas. Data from our study endorses the hypothesis that HPV infection promotes formation of sinonasal papillomas. However, apart from HPV genotypes that are frequently found in e.g. anogenital lesions (such as 6, 11, or 16), tissue samples of sinonasal papillomas also displayed infection with "rare" HPV types (such as 58, 42, 83, or 91).
Asunto(s)
Neoplasias Nasales/virología , Papiloma/virología , Infecciones por Papillomavirus/genética , Neoplasias de los Senos Paranasales/virología , Genotipo , Humanos , Neoplasias Nasales/patología , Papiloma/patología , Papillomaviridae/genética , Neoplasias de los Senos Paranasales/patología , Estudios RetrospectivosAsunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Conjuntiva/terapia , Crioterapia , Papillomavirus Humano 6/aislamiento & purificación , Procedimientos Quirúrgicos Oftalmológicos , Papiloma/terapia , Infecciones por Papillomavirus/terapia , Preescolar , Terapia Combinada , Neoplasias de la Conjuntiva/virología , Femenino , Humanos , Interferón alfa-2/uso terapéutico , Papiloma/virología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la PolimerasaRESUMEN
Laryngeal papillomas (LP) is a difficult disease to manage due to its frequent recurrence, airway compromise, and risk of cancer. Recently, growing evidence indicates the aberrant expression of OGFPD1, a stress granule protein, links closely to the development of tumorigenesis; however, little is known about its role in LP progression. Here, we investigated the tumor promoting action of OGFOD1 in LP. The transcriptional and translational levels of OGFOD1 were significantly up-regulated in LP tissues and cells. Moreover, OGFOD1 promoted viability and proliferation, and inhibited LP cells apoptosis. We further revealed that OGFOD1 was directly targeted by miR-1224-5p, which was significantly down-regulated in LP. Overexpression of the miR-1224-5p suppressed OGFOD1-induced cell proliferation and viability, and promoted apoptosis of LP. In accordance, knockdown of miR-1224-5p inversed the inhibitory effects. In confederation of the central involvement of OGFOD1 in LP progression, targeting the miR-1224-5p/OGFOD1 pathway might provide a novel strategy for LP treatment.
Asunto(s)
Proteínas Portadoras/metabolismo , Proliferación Celular , Neoplasias Laríngeas/patología , MicroARNs/genética , Proteínas Nucleares/metabolismo , Papiloma/patología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Apoptosis , Proteínas Portadoras/genética , China/epidemiología , Regulación Neoplásica de la Expresión Génica , Humanos , Incidencia , Neoplasias Laríngeas/epidemiología , Neoplasias Laríngeas/virología , Proteínas Nucleares/genética , Papiloma/epidemiología , Papiloma/virología , Infecciones por Papillomavirus/virología , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To characterize inflammatory cells in Recurrent Respiratory Papillomatosis (RRP) and to correlate it with severity using the Derkay laryngoscopic scale. MATERIALS AND METHODS: The data and biopsies from 36 patients with Juvenile (JRRP) and 56 patients with Adult (ARRP) were collected and analyzed under light microscopy. The patients were separated into groups according to the Derkay index: ≥20 for the most severe and < 20 for the less severe cases. Immunohistochemical analysis using CD3, CD4, CD8, CD15, CD20, CD68, FoxP3 and MUM-1 antibodies was performed, and the inflammatory cells were quantified. All the clinicopathological characteristics and the results of the immunohistochemical analysis were compared among the groups proposed using the Chi-Square test and correlated through the Spearman correlation test. RESULTS: The ARRP showed significantly higher quantities of CD3+, CD8+ and MUM1+ cells (p < .05) than the JRRP samples. The presence of CD15+ cells showed positive correlation with the Derkay index (p < .05), while the MUM-1+ cells showed an inverse correlation (p = .01). CONCLUSION: There are differences between the inflammatory cells population in the juvenile and adult groups and it can be related to disease severity.
Asunto(s)
Papiloma/patología , Neoplasias del Sistema Respiratorio/patología , Adulto , Autoanticuerpos , Complejo CD3 , Antígenos CD4 , Antígenos CD8 , Niño , Preescolar , Femenino , Humanos , Lactante , Inflamación , Factores Reguladores del Interferón/inmunología , Laringoscopía , Antígeno Lewis X , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Papiloma/metabolismo , Papiloma/virología , Papillomaviridae , Neoplasias del Sistema Respiratorio/metabolismo , Neoplasias del Sistema Respiratorio/virología , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE AND METHODS: A retrospective study was conducted to identify and assess potential clinical and molecularbiological risk factors for development and recurrence of sinonasal papillomas (i.e. inverted (IP), fungiform (FP), and oncocytic papillomas (OCP)). Investigated risk factors included age, gender, tumor size and localization, tobacco smoking, regular alcohol consumption, essential hypertension, anticoagulant medication, allergies, surgical approach, and HPV infection. Risk factors were evaluated by regression analysis. RESULTS: Apart from age and incomplete tumor resection, the recurrence of Schneiderian papillomas is independent of conventional risk factors. Patients in this study displayed higher HPV infections rates in IP (38.8%) and in FP (100%) than in healthy mucosa, which is reported 0-5.8% in Germany and central Europe. The proportion of HPV-positive IP decreased with advanced tumor stages: 100% HPV positivity of T1 IP (2/2), 40.9% of T2 IP (9/22), and 35.7% of T3 IP (20/56). Most commonly detected HPV types were HPV 6, 11, and 16; however, patients in this study also displayed HPV types that have rarely or not at all been described in sinonasal papillomas before, such as HPV 58, 42, 83, and 91. Recurrent sinonasal papillomas displayed higher rates of HPV infections than non-recurrent tumors. CONCLUSIONS: Young age at initial diagnosis and incomplete tumor resection are risk factors for recurrence of sinonasal papillomas. Our data suggest that HPV infection supports development and/or perpetuation of sinonasal papillomas. Additionally, sinonasal papillomas seem to display a unique subset of HPV genotypes, including genotypes that have not often been described before.