RESUMEN

Merkel cell polyomavirus (MCPyV) is a significant contributor to the development of Merkel cell carcinoma (MCC), an aggressive skin cancer with high recurrence and a low survival rate. In fact, it is the deadliest skin cancer. The precise routes of transmission for MCPyV-positive MCC remain unclear, but several factors may trigger its development. Conventional treatments for MCC are not highly effective, especially in patients with metastasis, with a clear need for new treatment options. Gene-targeted therapies hold great promise for the treatment of MCC, including the use of siRNA and CRISPR/Cas (C/Cas) but critically none have yet been translated into clinical trials. Validating this approach is the fact that several siRNA products are already FDA licenced, while C/Cas has entered clinical trial, albeit for conditions other than MCC. There are many challenges that must be overcome to move from preclinical research to the clinic. In this review, we provide a comprehensive summary of the current understanding of MCC, with a particular focus on MCPyV-positive MCC, and the status of gene-targeted therapies. Additionally, we discuss the major obstacles that impede MCC research and explore future prospects.

Asunto(s)

Carcinoma de Células de Merkel , Terapia Genética , Poliomavirus de Células de Merkel , Infecciones por Polyomavirus , Humanos , Poliomavirus de Células de Merkel/genética , Carcinoma de Células de Merkel/virología , Carcinoma de Células de Merkel/terapia , Carcinoma de Células de Merkel/genética , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/terapia , Terapia Genética/métodos , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/virología , Neoplasias Cutáneas/genética , Animales , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/terapia , ARN Interferente Pequeño/genética

RESUMEN

AIMS: This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients. METHODS: In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus. FINDINGS: HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs. CONCLUSION: Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies.

Asunto(s)

Virus BK , Infecciones por Citomegalovirus , Citomegalovirus , Infecciones por Virus de Epstein-Barr , Rechazo de Injerto , Herpesvirus Humano 4 , Trasplante de Riñón , Infecciones por Polyomavirus , Carga Viral , Viremia , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Virus BK/aislamiento & purificación , Virus BK/genética , Adulto , Estudios Transversales , Infecciones por Polyomavirus/virología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Citomegalovirus/virología , Citomegalovirus/aislamiento & purificación , Citomegalovirus/genética , Rechazo de Injerto/virología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Irán/epidemiología , Factores de Riesgo , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/sangre , Anciano , Adulto Joven , Receptores de Trasplantes/estadística & datos numéricos

RESUMEN

AIM: The objective of this study was to investigate the pooled prevalence and possible association between polyomavirus infection and lung cancer. METHODS: A systematic publication search was conducted by identifying relevant cross-sectional and case-control studies from major online databases. Heterogeneity, OR, and corresponding 95 % CI were applied to all studies through meta-analysis and forest plot. Random effects models were used to calculate the overall pooled prevalence. Visual inspection of a funnel plot plotting the log-transformed OR and its associated standard error of the log (OR) was combined with the Begg and Egger test to examine the presence and influence of publication bias. Analyzes were performed using Stata software v.14.1. RESULTS: 23 articles (33 datasets) were included in the meta-analysis, of which 14 datasets were case/control and the rest were cross-sectional studies. The pooled polyomavirus infection rate in lung cancer patients was 0.06 % (0.02-0.11 %). In subgroup analysis, the pooled prevalence of JCV, MCPyV, KI, SV40, BKV, WU, MU, and STL was 21 %, 7 %, 6 %, 2 %, 0 %, 0 %, 0 %, and 0 % respectively. An association has been found between polyomavirus infection and lung cancer [summary OR 6.33 (95 % CI (1.76-22.77); I2=67.45 %)]. The subgroup analysis, based on the virus type, showed a strong association between MCPyV and lung cancer [summary OR 13.61 (95 % CI 2.41-76.59; I2=40.0 %)]. despite the high prevalence of JCV DNA in lung cancer tissue, analysis of case-control studies showed that JCV is not associated with lung cancer and does not increase the risk of lung cancer. CONCLUSION: This study showed a significant association between polyomaviruses infection with lung cancer. The results also revealed a pooled prevalence of 6 % for polyomaviruses in lung tumor patients. Altogether, the findings of the present work suggest that Merkel cell polyomavirus infection is a potential risk factor for lung cancer.

Asunto(s)

Neoplasias Pulmonares , Infecciones por Polyomavirus , Humanos , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/virología , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/virología , Prevalencia , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/complicaciones , Poliomavirus/aislamiento & purificación

RESUMEN

Merkel cell carcinoma (MCC) is an extremely rare cutaneous neuroendocrine cancer, with an incidence approximately 40 times lower than that of malignant melanoma; however, its significantly inferior survival rate compared to melanoma establishes MCC as the most lethal form of skin cancer. In recent years, a substantial body of literature has demonstrated a gradual increase in the incidence of MCC. Although the two factors that contribute to MCC, ultraviolet radiation and Merkel cell polyomavirus infection, have been well established, the specific pathogenesis of this disease remains unclear. Additionally, considering the high lethality and recurrence rates of MCC, as well as the absence of specific antitumor drugs, it is crucial to elucidate the factors that can accurately predict patients' outcomes. In this review, we summarized the significant advancements in the epidemiological characteristics, pathogenesis, and the factors that influence patient prognosis of MCC to enhance clinical practices and public health efforts.

Asunto(s)

Carcinoma de Células de Merkel , Poliomavirus de Células de Merkel , Infecciones por Polyomavirus , Neoplasias Cutáneas , Carcinoma de Células de Merkel/epidemiología , Carcinoma de Células de Merkel/virología , Carcinoma de Células de Merkel/patología , Humanos , Pronóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/virología , Neoplasias Cutáneas/patología , Poliomavirus de Células de Merkel/genética , Poliomavirus de Células de Merkel/aislamiento & purificación , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/complicaciones , Incidencia , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/virología , Rayos Ultravioleta

RESUMEN

The objective of this study was to categorise diseases associated with FeLV infection in cats. A total of 154 cats were submitted to necropsy, histopathology exam and anti-FeLV immunohistochemistry (IHC), and 83 (50.9 %) were IHC FeLV-positive. The cats age means of 4.1 years, including 3.6 % kittens, 34.9 % junior, 37.4 % prime, 18.1 % mature, 2.4 % senior, 3.6 % unknown age. Neoplastic diseases were most prevalent with leukaemia and lymphoma being most predominant, followed by viral diseases, bacterial, trauma, degenerative, intoxications, parasitic, malformation and others. FeLV+ cats were 5.73 times more likely to be diagnosed with neoplasms than other diseases. The odds ratio (OR) of FeLV+ cats developing leukaemia (OR = 7.75) and lymphoma (OR = 6.75) was higher than other neoplasms. FeLV infection was more prevalent in the mixed breed, junior to prime, male, with neoplastic diseases, including leukaemia and lymphoma. Therefore, understanding the diseases associated with FeLV is of paramount importance in Brazil due to its high prevalence, and it may encourage the implementation of prophylactic measures to reduce its dissemination.

Asunto(s)

Enfermedades de los Gatos , Virus de la Leucemia Felina , Leucemia Felina , Gatos , Animales , Virus de la Leucemia Felina/aislamiento & purificación , Brasil/epidemiología , Masculino , Enfermedades de los Gatos/virología , Enfermedades de los Gatos/epidemiología , Femenino , Prevalencia , Leucemia Felina/epidemiología , Leucemia Felina/virología , Linfoma/epidemiología , Linfoma/veterinaria , Linfoma/virología , Infecciones por Retroviridae/epidemiología , Infecciones por Retroviridae/veterinaria , Infecciones por Retroviridae/virología , Inmunohistoquímica , Neoplasias/epidemiología , Neoplasias/veterinaria , Neoplasias/virología , Infecciones Tumorales por Virus/veterinaria , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/virología

RESUMEN

Despite the high prevalence of BK polyomavirus (BKPyV) and the associated risk for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant (KTX) recipients, many details on viral processes such as replication, maturation, assembly and virion release from host cells have not been fully elucidated. VP1 is a polyomavirus-specific protein that is expressed in the late phase of its replicative cycle with important functions in virion assembly and infectious particle release. This study investigated the localization and time-dependent changes in the distribution of VP1-positive viral particles and their association within the spectrum of differing cell morphologies that are observed in the urine of KTX patients upon active BKPyV infection. We found highly differing recognition patterns of two anti-VP1 antibodies with respect to intracellular and extracellular VP1 localization, pointing towards independent binding sites that were seemingly associated with differing stages of virion maturation. Cells originating from single clones were stably cultured out of the urine sediment of KTX recipients with suspected BKPyVAN. The cell morphology, polyploidy, virus replication and protein production were investigated by confocal microscopy using both a monoclonal (mAb 4942) and a polyclonal rabbit anti-VP1-specific antibody (RantiVP1 Ab). Immunoblotting was performed to investigate changes in the VP1 protein. Both antibodies visualized VP1 and the mAb 4942 recognized VP1 in cytoplasmic vesicles exhibiting idiomorphic sizes when released from the cells. In contrast, the polyclonal antibody detected VP1 within the nucleus and in cytoplasm in colocalization with the endoplasmic reticulum marker CNX. At the nuclear rim, VP1 was recognized by both antibodies. Immunoblotting revealed two smaller versions of VP1 in urinary decoy cell extracts, potentially from different translation start sites as evaluated by in silico analysis. Oxford Nanopore sequencing showed integration of BKPyV DNA in chromosomes 3, 4 and 7 in one of the five tested primary cell lines which produced high viral copies throughout four passages before transcending into senescence. The different staining with two VP1-specific antibodies emphasizes the modification of VP1 during the process of virus maturation and cellular exit. The integration of BKPyV into the human genome leads to high virus production; however, this alone does not transform the cell line into a permanently cycling and indefinitely replicating one.

Asunto(s)

Virus BK , Vesículas Extracelulares , Infecciones por Polyomavirus , Esparcimiento de Virus , Virus BK/fisiología , Virus BK/metabolismo , Virus BK/genética , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/virología , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/metabolismo , Replicación Viral , Trasplante de Riñón , Virión/metabolismo , Proteínas de la Cápside/metabolismo , Proteínas de la Cápside/genética , Núcleo Celular/metabolismo , Ensamble de Virus , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/metabolismo , Transformación Celular Viral , Masculino , Animales

RESUMEN

BACKGROUND: Several studies have reported the presence of JC virus (JCV) in human tumors, The association of JCV and CRC remains controversial. This study aimed to evaluate the rearranged NCCR region of the detected JCV DNA in CRC patients' tissue samples. METHODS: In this case-control study, tumor tissues (n = 60), adjacent normal tissues (n = 60), and urine samples (n = 60) of the CRC patients were collected. The nested PCR was employed to detect the VP1 and NCCR regions of the JCV genome. The positive JCV PCR products were sequenced and a phylogenetic tree was constructed to determine the JCV genotypes. After extracting RNA and preparing cDNA, the expression of JCV LTAg was examined in 60 tumor tissues and 60 adjacent normal tissues. The analysis of JCV LTAg expression was performed using GraphPad Prism software version 8. RESULTS: The analysis reveals that JCV DNA was detected in 35/60 (58.3%) tumor tissues, while 36/60 (60.0%) of adjacent normal tissues (p = 0.85). JCV DNA was detected in 42/60 (70.0%) urine samples when compared to 35/60 (58.3%) tumor tissues of CRC patients and was not found significant (P = 0.25). The phylogenetic tree analysis showed the dominant JCV genotype 3, followed by genotype 2D was distributed in tumor tissue, normal tissue, and urine samples of the CRC patients. Analysis of randomly selected NCCR sequences from JCV regions in tumor tissue samples revealed the presence of rearranged NCCR blocks of different lengths.: 431 bp, 292 bp, 449 bp, and 356 bp. These rearranged NCCR blocks differ from the rearranged NCCR blocks described in PML-type Mad-1, Mad-4, Mad-7, and Mad-8 prototypes. The expression of JCV LTAg was significantly different in tumor tissue compared to normal tissue, with a p-value of less than 0.002. CONCLUSION: A significant proportion of 35%> of the tumor tissue and urine samples of the CRC patients was found to be positive for JCV DNA (P = 0.25). The parallel analysis of tumor and urine samples for JCV DNA further supports the potential for non-invasive screening tools. This study provides new insights into Rearranged NCCR variant isolates from patients with CRC. The significant difference in JCV LTAg expression between tumor and normal tissue indicates a latent JCV status potentially leading to cancer development.

Asunto(s)

Neoplasias Colorrectales , ADN Viral , Virus JC , Filogenia , Humanos , Virus JC/genética , Virus JC/aislamiento & purificación , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Colorrectales/virología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/orina , ADN Viral/orina , ADN Viral/genética , Estudios de Casos y Controles , Anciano , Adulto , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/orina , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/orina , Reordenamiento Génico , Genotipo , Anciano de 80 o más Años

RESUMEN

Merkel cell polyomavirus (MCPyV) is the causative agent of the majority of Merkel cell carcinomas (MCC). The virus has limited coding capacity, with its early viral proteins, large T (LT) and small T (sT), being multifunctional and contributing to infection and transformation. A fundamental difference in early viral gene expression between infection and MCPyV-driven tumorigenesis is the expression of a truncated LT (LTtr) in the tumor. In contrast, sT is expressed in both conditions and contributes significantly to oncogenesis. Here, we identified novel functions of early viral proteins by performing genome-wide transcriptome and chromatin studies in primary human fibroblasts. Due to current limitations in infection and tumorigenesis models, we mimic these conditions by ectopically expressing sT, LT or LTtr, individually or in combination, at different time points. In addition to its known function in cell cycle and inflammation modulation, we reveal a fundamentally new function of sT. We show that sT regulates the type I interferon (IFN) response downstream of the type I interferon receptor (IFNAR) by interfering with the interferon-stimulated gene factor 3 (ISGF3)-induced interferon-stimulated gene (ISG) response. Expression of sT leads to a reduction in the expression of interferon regulatory factor 9 (IRF9) which is a central component of the ISGF3 complex. We further show that this function of sT is conserved in BKPyV. We provide a first mechanistic understanding of which early viral proteins trigger and control the type I IFN response, which may influence MCPyV infection, persistence and, during MCC progression, regulation of the tumor microenvironment.

Asunto(s)

Carcinoma de Células de Merkel , Evasión Inmune , Interferón Tipo I , Poliomavirus de Células de Merkel , Infecciones por Polyomavirus , Transducción de Señal , Infecciones Tumorales por Virus , Humanos , Poliomavirus de Células de Merkel/inmunología , Interferón Tipo I/metabolismo , Interferón Tipo I/inmunología , Carcinoma de Células de Merkel/virología , Carcinoma de Células de Merkel/inmunología , Transducción de Señal/inmunología , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/virología , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virología , Evasión Inmune/inmunología , Antígenos Virales de Tumores/metabolismo , Antígenos Virales de Tumores/inmunología , Antígenos Virales de Tumores/genética , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/virología , Neoplasias Cutáneas/metabolismo , Fibroblastos/virología , Fibroblastos/metabolismo , Fibroblastos/inmunología

RESUMEN

Renal transplantation is one of the primary approaches for curing end-stage kidney disease. With advancements in immunosuppressive agents, the short-term and long-term survival rates of transplanted kidneys have significantly improved. However, infections associated with potent immunosuppression have remained a persistent challenge. Among them, BK virus (BKV) reactivation following renal transplantation leading to BK virus-associated nephropathy (BKVAN) is a major cause of graft dysfunction. However, we still face significant challenges in understanding the pathogenesis, prevention, diagnosis, and treatment of BKVAN. These challenges include: 1. The mechanism of BKV reactivation under immunosuppressive conditions has not been well elucidated, leading to difficulties in breakthroughs in clinical research on prevention, diagnosis, and treatment. 2. Lack of proper identification of high-risk individuals, and effective personalized clinical management strategies. 3.Lack of early and sensitive diagnostic markers. 4. Lack of direct and effective treatment options due to the absence of specific antiviral drugs. The purpose of this review is to summarize the current status and cutting-edge advancements in BKV-related research, providing new methods and perspectives to address future research challenges.

Asunto(s)

Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/inmunología , Infecciones Tumorales por Virus/tratamiento farmacológico , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virología , Animales , Activación Viral , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Antivirales/uso terapéutico

RESUMEN

Replication of the complex retrovirus mouse mammary tumor virus (MMTV) is antagonized by murine Apobec3 (mA3), a member of the Apobec family of cytidine deaminases. We have shown that MMTV-encoded Rem protein inhibits proviral mutagenesis by the Apobec enzyme, activation-induced cytidine deaminase (AID) during viral replication in BALB/c mice. To further study the role of Rem in vivo, we have infected C57BL/6 (B6) mice with a superantigen-independent lymphomagenic strain of MMTV (TBLV-WT) or a mutant strain that is defective in Rem and its cleavage product Rem-CT (TBLV-SD). Compared to BALB/c, B6 mice were more susceptible to TBLV infection and tumorigenesis. Furthermore, unlike MMTV, TBLV induced T-cell tumors in B6 µMT mice, which lack membrane-bound IgM and conventional B-2 cells. At limiting viral doses, loss of Rem expression in TBLV-SD-infected B6 mice accelerated tumorigenesis compared to TBLV-WT in either wild-type B6 or AID-knockout mice. Unlike BALB/c results, high-throughput sequencing indicated that proviral G-to-A or C-to-T mutations were unchanged regardless of Rem expression in B6 tumors. However, knockout of both AID and mA3 reduced G-to-A mutations. Ex vivo stimulation showed higher levels of mA3 relative to AID in B6 compared to BALB/c splenocytes, and effects of agonists differed in the two strains. RNA-Seq revealed increased transcripts related to growth factor and cytokine signaling in TBLV-SD-induced tumors relative to TBLV-WT-induced tumors, consistent with another Rem function. Thus, Rem-mediated effects on tumorigenesis in B6 mice are independent of Apobec-mediated proviral hypermutation.

Asunto(s)

Citidina Desaminasa , Virus del Tumor Mamario del Ratón , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Infecciones por Retroviridae , Animales , Ratones , Virus del Tumor Mamario del Ratón/genética , Citidina Desaminasa/genética , Citidina Desaminasa/metabolismo , Infecciones por Retroviridae/inmunología , Infecciones por Retroviridae/virología , Infecciones por Retroviridae/genética , Ratones Noqueados , Replicación Viral , Infecciones Tumorales por Virus/genética , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/inmunología , Femenino , Desaminasas APOBEC/genética , Desaminasas APOBEC/metabolismo , Carcinogénesis/genética , Mutación

RESUMEN

Small extracellular vesicles (sEV) are small membrane-bound nanovesicles with a size range below 200 nm that are released by all types of cells. sEV carry a diverse cargo of proteins, lipids, glycans, and nucleic acids that mimic the content of producer cells. sEV mediate intercellular communication and play a key role in a broad variety of physiological and pathological conditions. Recently, numerous reports have emerged examining the role of sEV in viral infections. A significant number of similarities in the sEV biogenesis pathways and the replication cycles of viruses suggest that sEV might influence the course of viral infections in diverse ways. Besides directly modulating virus propagation by transporting the viral cargo (complete virions, proteins, RNA, and DNA), sEV can also modify the host antiviral response and increase the susceptibility of cells to infection. The network of mutual interactions is particularly complex in the case of oncogenic viruses, deserving special consideration because of its significance in cancer progression. This review summarizes the current knowledge of interactions between sEV and oncogenic viruses, focusing on sEV abilities to modulate the carcinogenic properties of oncoviruses.

Asunto(s)

Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/virología , Humanos , Animales , Virus Oncogénicos/fisiología , Replicación Viral , Neoplasias/virología , Infecciones Tumorales por Virus/virología , Interacciones Huésped-Patógeno

RESUMEN

Human papillomavirus (HPV) is an important causative factor of cervical cancer and is associated with nonsmall cell lung cancer (NSCLC). Merkel cell polyomavirus (MCPyV) is a rare and highly fatal cutaneous virus that can cause Merkel cell carcinoma (MCC). Although coinfection with oncogenic HPV and MCPyV may increase cancer risk, a definitive etiological link has not been established. Recently, genomic variation and genetic diversity in the MCPyV noncoding control region (NCCR) among ethnic groups has been reported. The current study aimed to provide accurate prevalence information on HPV and MCPyV infection/coinfection in NSCLC patients and to evaluate and confirm Korean MCPyV NCCR variant genotypes and sequences. DNA from 150 NSCLC tissues and 150 adjacent control tissues was assessed via polymerase chain reaction (PCR) targeting regions of the large T antigen (LT-ag), viral capsid protein 1 (VP1), and NCCR. MCPyV was detected in 22.7% (34 of 150) of NSCLC tissues and 8.0% (12 of 150) of adjacent tissues from Korean patients. The incidence rates of HPV with and without MCPyV were 26.5% (nine of 34) and 12.9% (15 of 116). The MCPyV NCCR genotype prevalence in Korean patients was 21.3% (32 of 150) for subtype I and 6% (nine of 150) for subtype IIc. Subtype I, a predominant East Asian strain containing 25 bp tandem repeats, was most common in the MCPyV NCCR data set. Our results confirm that coinfection with other tumor-associated viruses is not associated with NSCLC. Although the role of NCCR rearrangements in MCPyV infection remains unknown, future studies are warranted to determine the associations of MCPyV NCCR sequence rearrangements with specific diseases.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Variación Genética , Genotipo , Poliomavirus de Células de Merkel , Infecciones por Papillomavirus , Humanos , Carcinoma de Pulmón de Células no Pequeñas/virología , Carcinoma de Pulmón de Células no Pequeñas/genética , Femenino , Poliomavirus de Células de Merkel/genética , Poliomavirus de Células de Merkel/aislamiento & purificación , Persona de Mediana Edad , Masculino , Anciano , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , República de Corea/epidemiología , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/complicaciones , Papillomaviridae/genética , Papillomaviridae/clasificación , Adulto , Coinfección/virología , Coinfección/epidemiología , Neoplasias Pulmonares/virología , Anciano de 80 o más Años , Prevalencia , ADN Viral/genética , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/complicaciones , Infecciones Tumorales por Virus/epidemiología , Reacción en Cadena de la Polimerasa , Virus del Papiloma Humano

RESUMEN

Knowledge of Human Polyomavirus (HPyV) infection in the anal area and its association with sexually transmitted infections such as Human Papillomavirus (HPV) and Human Immunodeficiency Virus (HIV) remains limited. Therefore, anal specimens from 150 individuals of both sexes were analyzed for screening purposes. HPV DNA was found in 50.7% of cases, with a predominance of high-risk (HR) genotypes. HPyV DNA was found in 39.3% of samples, with Merkel Cell Polyomavirus (MCPyV) being the most common, with a higher viral load than JCPyV and BKPyV. In addition, MCPyV viral load increased in people living with HIV (PLWH) with HPV infection (p < 0.0001).

Asunto(s)

Coinfección , Infecciones por VIH , Poliomavirus de Células de Merkel , Infecciones por Papillomavirus , Infecciones por Polyomavirus , Carga Viral , Humanos , Masculino , Femenino , Infecciones por VIH/virología , Infecciones por VIH/complicaciones , Infecciones por Papillomavirus/virología , Adulto , Persona de Mediana Edad , Coinfección/virología , Coinfección/epidemiología , Poliomavirus de Células de Merkel/genética , Poliomavirus de Células de Merkel/aislamiento & purificación , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/epidemiología , ADN Viral/genética , Genotipo , Canal Anal/virología , Canal Anal/patología , Anciano , Adulto Joven , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/epidemiología , Prevalencia

Asunto(s)

Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus , Guías de Práctica Clínica como Asunto , Infecciones Tumorales por Virus , Humanos , Trasplante de Riñón/efectos adversos , Virus BK/patogenicidad , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/diagnóstico , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/virología , Consenso , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Antivirales/uso terapéutico

Asunto(s)

Corticoesteroides , Virus BK , Inmunosupresores , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Virus BK/inmunología , Virus BK/patogenicidad , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/virología , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virología , Corticoesteroides/uso terapéutico , Trasplante de Riñón , Resultado del Tratamiento , Factores de Riesgo

RESUMEN

While Merkel cell polyomavirus (MCPyV or MCV) is an abundant virus frequently shed from healthy skin, it is one of the most lethal tumor viruses in immunocompromised individuals, highlighting the crucial role of host immunity in controlling MCPyV oncogenic potential. Despite its prevalence, very little is known about how MCPyV interfaces with the host immune response to maintain asymptomatic persistent infection and how inadequate control of MCPyV infection triggers MCC tumorigenesis. In this study, we discovered that the MCPyV protein, known as the Alternative Large Tumor Open Reading Frame (ALTO), also referred to as middle T, effectively primes and activates the STING signaling pathway. It recruits Src kinase into the complex of STING downstream kinase TBK1 to trigger its autophosphorylation, which ultimately activates the subsequent antiviral immune response. Combining single-cell analysis with both loss- and gain-of-function studies of MCPyV infection, we demonstrated that the activity of ALTO leads to a decrease in MCPyV replication. Thus, we have identified ALTO as a crucial viral factor that modulates the STING-TBK1 pathway, creating a negative feedback loop that limits viral infection and maintains a delicate balance with the host immune system. Our study reveals a novel mechanism by which a tumorigenic virus-encoded protein can link Src function in cell proliferation to the activation of innate immune signaling, thereby controlling viral spread, and sustaining persistent infection. Our previous findings suggest that STING also functions as a tumor suppressor in MCPyV-driven oncogenesis. This research provides a foundation for investigating how disruptions in the finely tuned virus-host balance, maintained by STING, could alter the fate of MCPyV infection, potentially encouraging malignancy.

Asunto(s)

Poliomavirus de Células de Merkel , Infecciones por Polyomavirus , Proteínas Serina-Treonina Quinasas , Infecciones Tumorales por Virus , Proteínas Serina-Treonina Quinasas/metabolismo , Infecciones por Polyomavirus/metabolismo , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/virología , Humanos , Infecciones Tumorales por Virus/metabolismo , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virología , Carcinoma de Células de Merkel/virología , Carcinoma de Células de Merkel/metabolismo , Proteínas de la Membrana/metabolismo , Transducción de Señal , Proteínas Virales/metabolismo , Replicación Viral , Neoplasias Cutáneas/virología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/inmunología , Animales

RESUMEN

BK polyomavirus-associated nephropathy (PyVAN) remains a serious threat for renal dysfunction and graft loss in kidney transplant recipients on immunosuppressive medication. In this study, a pilot cohort of 16 kidney transplant recipients were recruited of which eight were with significant BKPV viremia (sBKPV) and the rest were controls matched to age, gender, and time since transplant. We used next-generation sequencing to characterize the miRNA expression profile in urine samples. In total, the expression of 8 miRNAs (miR-16-5p,miR-200c-3p,bkv-miR-B1-3p,let-7b-3p,miR-1269b,bkv-miR-B1-5p,miR-193a-3p,miR-944) were upregulated whereas 21miRNAs (miR-134-5p,miR-4724-5p,miR-127-3p,miR-6500-3p,miR-507,miR-378b,miR-3911,miR-211-5p,miR-486-5p,miR-143-3p,miR-3195,miR-1307-5p,miR-29a-5p,miR-378f,miR-12136,miR-378g,miR-144-3p,miR-378a-3p,let-7i-5p,miR-204-5p,miR-146a-5p) were downregulated with fold change > 2. We found that bkv-miR-B1-5p and bkv-miR-B1-3p have 19-fold and 5-fold higher expression values in BKPV viremia patient samples, respectively. A few earlier studies have reported BKV miRNA in urine and serum samples using the RT- PCR from PyVAN patients. Our results corroborated findings from earlier studies and highlighted the need for additional evaluation of the role of sequencing approaches for monitoring BKPV specific and host miRNAs to better understand the viral reactivation and disease pathogenesis.

Asunto(s)

Virus BK , Trasplante de Riñón , MicroARNs , Infecciones por Polyomavirus , Humanos , Trasplante de Riñón/efectos adversos , Virus BK/genética , Virus BK/aislamiento & purificación , MicroARNs/genética , MicroARNs/sangre , Infecciones por Polyomavirus/virología , Masculino , Persona de Mediana Edad , Femenino , Adulto , Infecciones Tumorales por Virus/virología , Proyectos Piloto

RESUMEN

Historically, to generate Simian Retrovirus (SRV) positive control materials, we performed in vivo passage by inoculating uninfected rhesus macaques with whole blood from an SRV-1 infected (antibody and PCR positive) macaque. However, recent attempts using this approach have failed. This study reports observations and explores why it has become more difficult to transmit SRV via in vivo passage.

Asunto(s)

Macaca mulatta , Enfermedades de los Monos , Infecciones por Retroviridae , Retrovirus de los Simios , Animales , Macaca mulatta/virología , Retrovirus de los Simios/aislamiento & purificación , Retrovirus de los Simios/fisiología , Infecciones por Retroviridae/veterinaria , Infecciones por Retroviridae/transmisión , Infecciones por Retroviridae/virología , Enfermedades de los Monos/virología , Enfermedades de los Monos/transmisión , Infecciones Tumorales por Virus/veterinaria , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/transmisión

RESUMEN

We present a challenging clinical case of a 68-year-old female kidney transplant recipient who had a complicated posttransplant course marked by borderline T-cell-mediated rejection and BK virus nephropathy. The treatment for borderline rejection with steroids resulted in overimmunosuppression, and the patient acquired cytomegalovirus infection manifesting as colitis and SARS-CoV-2 infection. This progressed rapidly to collapsing glomerulopathy and allograft failure. This study also highlights the challenges in surveillance with donor-derived cell-free DNA in the setting of allograft injury by multiple viral infections.

Asunto(s)

Virus BK , COVID-19 , Infecciones por Citomegalovirus , Rechazo de Injerto , Trasplante de Riñón , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Femenino , COVID-19/complicaciones , COVID-19/inmunología , COVID-19/diagnóstico , Anciano , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/diagnóstico , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/tratamiento farmacológico , Rechazo de Injerto/inmunología , Rechazo de Injerto/virología , Virus BK/patogenicidad , Virus BK/inmunología , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/diagnóstico , Progresión de la Enfermedad , Resultado del Tratamiento , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Coinfección

RESUMEN

Guidelines recommend monitoring of Epstein-Barr virus (EBV) and BK virus (BKV) in solid organ and hematopoietic stem cell transplant patients. The majority of quantitative DNA testing for EBV and BKV employs unstandardized individual laboratory-developed testing solutions (LDTs), with implications for accuracy, reproducibility, and comparability between laboratories. The performance of the cobas EBV and cobas BKV assays was assessed across five laboratories, using the World Health Organization International Standards (WHO IS) for EBV and BKV, and the National Institute of Standards and Technology Quantitative Standard for BKV, and results were compared with the LDTs in use at the time. Methods were also compared using locally sourced clinical specimens. Variation was high when laboratories reported EBV or BKV DNA values using LDTs, where quantitative values were observed to differ by up to 1.5 log10 unit/mL between sites. Conversely, results from the cobas EBV and cobas BKV assays were accurate and reproducible across sites and on different testing days. Adjustment of LDTs using the international standards led to closer alignment between the assays; however, day-to-day reproducibility of LDTs remained high. In addition, BKV continued to show bias, indicating challenges with the commutability of the BKV International Standard. The cobas EBV and cobas BKV assays are automated, aligned to the WHO IS, and have the potential to reduce the variability in viral load testing introduced by differences in LDTs. Standardization of reporting values may eventually allow different centers to compare data to allow clinical decision thresholds to be established supporting improvements in patient management.IMPORTANCEThe application of center-specific cut-offs for clinical decisions and the variability of LDTs often hinder interpretation; thus, the findings reported here support the need for standardization in the field of post-transplant monitoring of EBV and BKV to improve patient management. Alongside the choice of assay, it is also important to consider which standard to use when deciding upon a testing methodology. This is a call to action for standardization, as treatment for EBV and BKV is driven by viral load test results, and the more accurate and comparable the test results are across institutions, the more informed and better the treatment decisions can be.

Asunto(s)

Virus BK , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Carga Viral , Humanos , Virus BK/aislamiento & purificación , Virus BK/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Carga Viral/normas , Carga Viral/métodos , Reproducibilidad de los Resultados , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/virología , ADN Viral/genética , ADN Viral/análisis , Técnicas de Diagnóstico Molecular/normas , Técnicas de Diagnóstico Molecular/métodos , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/virología