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1.
BMC Pediatr ; 24(1): 200, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515059

RESUMO

BACKGROUND: The results of disparate clinical studies indicate abnormally frequent cases of certain microorganisms in children with autism spectrum disorders (ASD). However, these data require clarification and systematization. The study aims to study the structure of the microbial profile in children with ASD and genetic folate cycle deficiency (GFCD) and consider differences in diagnostic approaches for identifying microorganisms of different types. METHODS: The study analyzed medical data from 240 children (187 boys and 63 girls) with GFCD aged 2 to 9 years. The children had clinical manifestations of ASD (the study group, SG). The control group (CG) included 53 clinically healthy children (37 boys and 16 girls) of the same age but without GFCD. Both groups of children were tested on active herpetic infections (HSV-1/2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8), ТТV, Streptococcus pyogenes, Candida albicans, Borrelia burgdorferi, Mycoplasma pneumoniae, Chlamydia pneumoniae, Yersinia enterocolitica, Toxoplasma gondii, congenital CMV neuroinfection and postnatal HSV-1/2 encephalitis. The testing used diagnostic methods specified in PubMed-indexed studies. RESULTS: In the SG, TTV was found in 196 children (82%), HHV-7 - in 172 (72%), HHV-6 - in 162 (68%), EBV - in 153 (64%), Streptococcus pyogenes - in 127 (53%), Candida albicans - in 116 (48%), Borrelia - in 107 (45%), Mycoplasma pneumoniae - in 94 (39%), Chlamydia pneumoniae - in 85 (35%), Yersinia entеrocolitica - in 71 (30%), Toxoplasma gondii - in 54 (23%), congenital CMV neuroinfection - in 26 (11%), and postnatal HSV-1/2 encephalitis - in 11 children (5% of cases) (p < p0.05; Z < Z0.05). In the SG, there was a higher microbial load in older children (p < p0.05; Z < Z0.05). No gender differences were found. CONCLUSIONS: The study described and characterized a specific abnormal microbial spectrum with a predominance of viral opportunistic agents in children with ASD associated with GFCD.


Assuntos
Transtorno do Espectro Autista , Infecções por Citomegalovirus , Encefalite , Infecções por Herpesviridae , Herpesvirus Humano 6 , Masculino , Criança , Feminino , Humanos , Infecções por Herpesviridae/diagnóstico , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/diagnóstico , Herpesvirus Humano 6/genética , Ácido Fólico
2.
J Med Case Rep ; 18(1): 81, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38424575

RESUMO

BACKGROUND: Human herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series. CASE PRESENTATION: In this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively. CONCLUSION: This case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient.


Assuntos
Herpesvirus Humano 6 , Linfo-Histiocitose Hemofagocítica , Transtornos Mentais , Adulto , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/complicações , Estado Terminal , Reação em Cadeia da Polimerase , Herpesvirus Humano 6/genética , Transtornos Mentais/complicações
3.
Intern Med J ; 54(3): 499-502, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38380836

RESUMO

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction where patients present with fever, morbilliform rash and multiorgan manifestations, which may include acute renal failure, acute respiratory distress syndrome and eosinophilic myocarditis. We present a case of a 60-year-old woman with acute heart failure, DRESS syndrome features and human herpesvirus 6 reactivation in the absence of a drug trigger. She was diagnosed with eosinophilic myocarditis and successfully treated with corticosteroid therapy.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Insuficiência Cardíaca , Herpesvirus Humano 6 , Miocardite , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico
4.
J Infect Dev Ctries ; 18(1): 152-157, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38377081

RESUMO

INTRODUCTION: Human herpesvirus 6B (HHV-6B) encephalitis is common in immunosuppressed patients and presents a diagnostic challenge for physicians. Metagenomic next-generation sequencing (mNGS) may facilitate early diagnosis of HHV-6B encephalitis. Herein, we described a case of HHV-6B encephalitis following transplantation for severe aplastic anemia (SAA) diagnosed by mNGS. CASE SUMMARY: A 31-year-old male underwent myeloablative haploid hematopoietic stem cell transplantation for the treatment of SAA. On day + 21 after transplantation, the patient developed symptoms such as sudden epilepsy, drowsiness, memory dislocation, and memory loss. HHV-6B encephalitis was confirmed based on cranial MRI and mNGS of cerebrospinal fluid. Following antiviral therapy with sodium foscarnet, the symptoms improved and HHV-6B was negative by mNGS. There were no serious sequelae. Currently, the patient is in good health and is still under follow-up. CONCLUSIONS: A case of HHV-6B encephalitis after SAA transplantation was diagnosed by mNGS of cerebrospinal fluid in time and was effectively treated with sodium foscarnet.


Assuntos
Anemia Aplástica , Encefalite Viral , Encefalite , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Infecções por Roseolovirus , Masculino , Humanos , Adulto , Foscarnet/uso terapêutico , Herpesvirus Humano 6/genética , Anemia Aplástica/terapia , Anemia Aplástica/complicações , Encefalite Viral/diagnóstico , Encefalite Viral/tratamento farmacológico , Encefalite Viral/líquido cefalorraquidiano , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/tratamento farmacológico , Infecções por Roseolovirus/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sequenciamento de Nucleotídeos em Larga Escala , Sódio
5.
Int J Hematol ; 119(4): 432-441, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38407786

RESUMO

This prospective multicenter study aimed to determine the effects of human herpesvirus-6B (HHV-6B) reactivation on central nervous system (CNS) function in cord blood transplant (CBT) recipients. Our focus was to track HHV-6B reactivation and evaluate its association with delirium and cognitive function, specifically in the domains of verbal memory, attention/processing speed, and quality of life (QOL). A cohort of 38 patients participated in this study. Of the 37 patients evaluated, seven (18.9%) developed delirium, with six of these cases emerging after HHV-6B reactivation (median lag, 7 days). Evaluation of verbal memory showed that the final trial score for unrelated words at 70 days after transplantation was significantly lower than that before preconditioning (P = 0.004) among patients (n = 15) who experienced higher-level HHV-6B reactivation (median or higher maximum plasma HHV-6 DNA load for participating patients). Patients without higher-level reactivation did not show significant declines in verbal memory scores. QOL was assessed using the 36-item Short-Form Health Survey, and the social functioning score 1 year post-transplantation was significantly lower in patients who experienced higher-level HHV-6B reactivation than in those who did not. Our findings suggest that higher-level HHV-6B reactivation can detrimentally affect certain cognitive functions in CBT recipients.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Delírio , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Humanos , Herpesvirus Humano 6/genética , Qualidade de Vida , Estudos Prospectivos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Ativação Viral , DNA Viral , Cognição
6.
J Med Virol ; 96(2): e29437, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38305059

RESUMO

Covid-19 in West Africa masked outbreaks of vaccine-preventable diseases such as the measles epidemic in children in Guinea in 2021-2022 characterized by a lack of confirmation of suspected clinical cases. During weeks 13-22 of 2022, saliva samples were collected from 213 children (3-60 months old) with measles-like symptoms within the St Gabriel dispensary in Conakry. Samples were processed in Virus Transport Medium (VTM) and tested on the same day by triplex reverse transcriptase -real-time polymerase chain reaction for Measles, Rubella and RNaseP. Samples were also tested for HHV6 and Parvovirus B19, viruses causing clinical signs similar to measles. We confirmed 146 (68.5%) measles cases, 27 (12.7%) rubella, 5 (2.3%) double-positive measles-rubella, 35 (16.4%) HHV-6 and 8 (3.75%) Parvovirus B19. To test the assay's robustness, 27 samples were kept at 26-30°C. Measles and rubella were still detected after 7 days at 26-30°C, and after 21 days measles and rubella were still detectable in all samples but one. Sequencing indicated the circulation of the B3 measles genotype, as expected in West Africa. This study highlights the robustness of the measles/rubella diagnostic test on saliva samples stored in VTM. The high level of rubella detection questioned the single valence measles vaccination strategy.


Assuntos
COVID-19 , Exantema , Herpesvirus Humano 6 , Sarampo , Parvovirus B19 Humano , Rubéola (Sarampo Alemão) , Criança , Humanos , Lactente , Pré-Escolar , Papua Nova Guiné , Anticorpos Antivirais , Imunoglobulina M , COVID-19/epidemiologia , COVID-19/complicações , Guiné , Vírus do Sarampo/genética , Parvovirus B19 Humano/genética
7.
Nat Commun ; 15(1): 542, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228644

RESUMO

Limited understanding of the immunopathogenesis of human herpesvirus 6B (HHV-6B) has prevented its acceptance as a pulmonary pathogen after hematopoietic cell transplant (HCT). In this prospective multicenter study of patients undergoing bronchoalveolar lavage (BAL) for pneumonia after allogeneic HCT, we test blood and BAL fluid (BALF) for HHV-6B DNA and mRNA transcripts associated with lytic infection and perform RNA-seq on paired blood. Among 116 participants, HHV-6B DNA is detected in 37% of BALs, 49% of which also have HHV-6B mRNA detection. We establish HHV-6B DNA viral load thresholds in BALF that are highly predictive of HHV-6B mRNA detection and associated with increased risk for overall mortality and death from respiratory failure. Participants with HHV-6B DNA in BALF exhibit distinct host gene expression signatures, notable for enriched interferon signaling pathways in participants clinically diagnosed with idiopathic pneumonia. These data implicate HHV-6B as a pulmonary pathogen after allogeneic HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Pneumonia , Infecções por Roseolovirus , Humanos , Herpesvirus Humano 6/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Prospectivos , Infecções por Roseolovirus/genética , Transcriptoma , DNA , Pneumonia/complicações , RNA Mensageiro
8.
J Neuroimmunol ; 387: 578283, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38184892

RESUMO

A case of the 'perfect storm' of myelin oligodendrocyte glycoprotein (MOG) antibody-mediated myelitis, human herpesvirus 6 (HHV-6) reactivation, and COVID-19 infection was reported in 2021. This article reports a case of a similarly observed clinical triad, but with a different conclusion and explanation supported by laboratory test results and evidence from our literature review.


Assuntos
Herpesvirus Humano 6 , Mielite , Neurite Óptica , Humanos , Herpesvirus Humano 6/genética , Autoanticorpos , Glicoproteína Mielina-Oligodendrócito
9.
EMBO Rep ; 25(2): 725-744, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177923

RESUMO

Viral infection often trigger an ATM serine/threonine kinase (ATM)-dependent DNA damage response in host cells that suppresses viral replication. Viruses evolved different strategies to counteract this antiviral surveillance system. Here, we report that human herpesvirus 6B (HHV-6B) infection causes genomic instability by suppressing ATM signaling in host cells. Expression of immediate-early protein 1 (IE1) phenocopies this phenotype and blocks homology-directed double-strand break repair. Mechanistically, IE1 interacts with NBS1, and inhibits ATM signaling through two distinct domains. HHV-6B seems to efficiently inhibit ATM signaling as further depletion of either NBS1 or ATM do not significantly boost viral replication in infected cells. Interestingly, viral integration of HHV-6B into the host's telomeres is not strictly dependent on NBS1, challenging current models where integration occurs through homology-directed repair. Given that spontaneous IE1 expression has been detected in cells of subjects with inherited chromosomally-integrated form of HHV-6B (iciHHV-6B), a condition associated with several health conditions, our results raise the possibility of a link between genomic instability and the development of iciHHV-6-associated diseases.


Assuntos
Herpesvirus Humano 6 , Proteínas Imediatamente Precoces , Infecções por Roseolovirus , Humanos , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/metabolismo , Infecções por Roseolovirus/genética , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Integração Viral , Instabilidade Genômica , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
10.
Brain ; 147(1): 177-185, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-37930324

RESUMO

Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A. A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI). Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis). In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 6 , Esclerose Múltipla , Humanos , Anticorpos , Biomarcadores , Estudos de Casos e Controles , Herpesvirus Humano 4 , Masculino , Feminino
12.
Sci Rep ; 13(1): 18654, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907711

RESUMO

Human Leukocyte Antigen (HLA) is involved in both multiple sclerosis (MS) and immune response to viruses. Here we investigated the virus-HLA immunogenicity (V-HLA) of 12 viruses implicated in MS with respect to 17 HLA Class I alleles positively associated to MS prevalence in 14 European countries. Overall, higher V-HLA immunogenicity was associated with smaller MS-HLA effect, with human herpes virus 3 (HHV3), JC human polyoma virus (JCV), HHV1, HHV4, HHV7, HHV5 showing the strongest association, followed by HHV8, HHV6A, and HHV6B (moderate association), and human endogenous retrovirus (HERV-W), HHV2, and human papilloma virus (HPV) (weakest association). These findings suggest that viruses with proteins of high HLA immunogenicity are eliminated more effectively and, consequently, less likely to be involved in MS.


Assuntos
Herpesvirus Humano 6 , Vírus JC , Esclerose Múltipla , Humanos , Imunogenética , Herpesvirus Humano 6/genética , Europa (Continente)
13.
Diagn Pathol ; 18(1): 124, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964347

RESUMO

AIMS: The association of human herpesvirus 6 (HHV-6) species with pancreatic cancer is controversially discussed. The aim of this study was to further investigate the postulated association and to identify the basis of HHV-6 DNA positivity reported for pancreatic cancer tissue. METHODS: All samples of patients with pancreatic cancer (cancer and surrounding tissue) were analyzed for presence of HHV-6 DNA by PCR and then selected cases by immunohistochemistry. RESULTS: Sixty eight per cent (68% = 52/77) of all patients were HHV-6 DNA positive in any of the samples, 49% (38/77) were positive in tumor tissue. Specimens of just one patient were HHV-6A DNA positive, all other patients were positive for HHV-6B. Immunohistochemical analysis of HHV-6 DNA positive samples did not reveal any specific HHV-6B protein positive tumor cell. In contrast, supposed immune cells presented intra- and peritumorally expressed HHV-6B-protein. The cause of presence of these cells in the tumor stroma is unknown, as of yet. CONCLUSIONS: HHV-6 DNA-positivity of pancreatic cancer tissue described by us and others is probably not due to the infection of pancreatic cells by HHV-6, but rather due to the migration of HHV-6 positive immune cells into the pancreas. Based on our data, we suppose that there is no direct evidence for HHV-6 as a causative agent of pancreatic cancer, but further in-depth studies (including investigation of immune status of patients) are necessary to make definitive conclusions.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Herpesvirus Humano 6 , Neoplasias Pancreáticas , Infecções por Roseolovirus , Humanos , Herpesvirus Humano 6/genética , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/genética , DNA Viral/genética , Neoplasias Pancreáticas
14.
Anal Chem ; 95(46): 17117-17124, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37943782

RESUMO

The detection of the U94 gene in human herpesvirus 6 is crucial for early diagnosis of HHV-6 infections, which could induce acute febrile illness in infants. In this work, the first ultrasensitive electrochemiluminescence (ECL) biosensor for detecting U94 gene in Human Herpesvirus 6 was successfully designed by utilizing efficient novel metal-organic framework (MOF)-based ECL nanoemitters comprising iridium(III) complexes (Ir-ZIF-8-NH2) synthesized via one-pot coordination reaction strategy as an ECL indicator and a target-catalyzed hairpin assembly (CHA) signal amplification strategy. The as-prepared ECL indicator Ir-ZIF-8-NH2 exhibited an approximately 2.7-fold ECL intensity compared with its small molecular analogue of emissive iridium(III) complex named IrppymIM formed by in situ coordination reaction between iridium(III) solvent complex and imidazole ligands. In addition, a target-catalyzed hairpin assembly (CHA) strategy was employed to further improve the sensitivity of the proposed ECL biosensor, which demonstrated a wide linear range from 1 fM to 1 µM and the limit of detection as low as 0.113 fM (S/N = 3). Significantly, this biosensor was successfully applied to detect U94 gene in plasmids and real virus samples. The recoveries were in the range of 97.0-109.0% for plasmids and 95.7-107.5% for real virus samples with a relative standard deviation (RSD) of 1.87-2.53%. These satisfactory experimental results from the proposed ECL biosensor in this work would inevitably promote the development of new time/cost-effective and sensitive methods to detect HHV-6 with a major global health threat and substantial burden on healthcare in the future.


Assuntos
Técnicas Biossensoriais , Herpesvirus Humano 6 , Estruturas Metalorgânicas , Humanos , Herpesvirus Humano 6/genética , Irídio , Técnicas Eletroquímicas/métodos , Medições Luminescentes/métodos , Técnicas Biossensoriais/métodos , Limite de Detecção
15.
Nature ; 623(7987): 608-615, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37938768

RESUMO

Cell therapies have yielded durable clinical benefits for patients with cancer, but the risks associated with the development of therapies from manipulated human cells are understudied. For example, we lack a comprehensive understanding of the mechanisms of toxicities observed in patients receiving T cell therapies, including recent reports of encephalitis caused by reactivation of human herpesvirus 6 (HHV-6)1. Here, through petabase-scale viral genomics mining, we examine the landscape of human latent viral reactivation and demonstrate that HHV-6B can become reactivated in cultures of human CD4+ T cells. Using single-cell sequencing, we identify a rare population of HHV-6 'super-expressors' (about 1 in 300-10,000 cells) that possess high viral transcriptional activity, among research-grade allogeneic chimeric antigen receptor (CAR) T cells. By analysing single-cell sequencing data from patients receiving cell therapy products that are approved by the US Food and Drug Administration2 or are in clinical studies3-5, we identify the presence of HHV-6-super-expressor CAR T cells in patients in vivo. Together, the findings of our study demonstrate the utility of comprehensive genomics analyses in implicating cell therapy products as a potential source contributing to the lytic HHV-6 infection that has been reported in clinical trials1,6-8 and may influence the design and production of autologous and allogeneic cell therapies.


Assuntos
Linfócitos T CD4-Positivos , Herpesvirus Humano 6 , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Ativação Viral , Latência Viral , Humanos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Ensaios Clínicos como Assunto , Regulação Viral da Expressão Gênica , Genômica , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/isolamento & purificação , Herpesvirus Humano 6/fisiologia , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Encefalite Infecciosa/complicações , Encefalite Infecciosa/virologia , Receptores de Antígenos Quiméricos/imunologia , Infecções por Roseolovirus/complicações , Infecções por Roseolovirus/virologia , Análise da Expressão Gênica de Célula Única , Carga Viral
16.
Viruses ; 15(10)2023 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-37896899

RESUMO

Recent studies have shown that thyrocytes are permissive to HHV-6A infection and that the virus may contribute to the pathogenesis of autoimmune thyroiditis. Thyroid autoimmune diseases increase the risk of papillary cancer, which is not surprising considering that chronic inflammation activates pathways that are also pro-oncogenic. Moreover, in this condition, cell proliferation is stimulated as an attempt to repair tissue damage caused by the inflammatory process. Interestingly, it has been reported that the well-differentiated papillary thyroid carcinoma (PTC), the less aggressive form of thyroid tumor, may progress to the more aggressive follicular thyroid carcinoma (FTC) and eventually to the anaplastic thyroid carcinoma (ATC), and that to such progression contributes the presence of an inflammatory/immune suppressive tumor microenvironment. In this study, we investigated whether papillary tumor cells (BCPAP) could be infected by human herpes virus-6A (HHV-6A), and if viral infection could induce effects related to cancer progression. We found that the virus dysregulated the expression of several microRNAs, such as miR-155, miR-9, and the miR-221/222 cluster, which are involved in different steps of carcinogenesis, and increased the secretion of pro-inflammatory cytokines, particularly IL-6, which may also sustain thyroid tumor cell growth and promote cancer progression. Genomic instability and the expression of PTEN, reported to act as an oncogene in mutp53-carrying cells such as BCPAP, also increased following HHV-6A-infection. These findings suggest that a ubiquitous herpesvirus such as HHV-6A, which displays a marked tropism for thyrocytes, could be involved in the progression of PTC towards more aggressive forms of thyroid tumor.


Assuntos
Carcinoma Papilar , Herpesvirus Humano 6 , MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide , Herpesvirus Humano 6/genética , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Microambiente Tumoral
17.
J Int Med Res ; 51(10): 3000605231204479, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37873767

RESUMO

We report a case of human herpes virus 6 (HHV-6)- and human herpes virus 7 (HHV-7)-associated choroiditis in an immunocompromised woman. A 42-year-old Chinese woman with a history of acute myelogenous leukemia presented with blurred vision and black floaters in her right eye. Anterior segment examination findings were normal. Ophthalmoscopic examination revealed a subretinal lesion in the superonasal peripapillary region with several punctate hemorrhages. Optical coherence tomography showed a crater-like choroidal protuberance, associated with retinal pigment epithelium rupture and full-thickness retinal edema in the involved area. Indocyanine green angiography demonstrated a broad hypofluorescent lesion in the choroid. The patient was diagnosed with choroiditis. Subsequently, metagenomic next-generation sequencing revealed HHV-6B and HHV-7 DNA in the aqueous humor. Therefore, antiviral therapy was initiated. The patient experienced resolution of all symptoms and signs after treatment with intravenous foscarnet and oral acyclovir. The findings in this case indicate that HHV-6 and HHV-7 can cause ocular infection, particularly in immunocompromised patients.


Assuntos
Corioidite , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Leucemia Mieloide Aguda , Humanos , Feminino , Adulto , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Corioidite/diagnóstico , Corioidite/patologia , Corioide/patologia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/patologia , Tomografia de Coerência Óptica
18.
J Med Virol ; 95(10): e29141, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37796084

RESUMO

In the quest to eliminate measles virus (MV) and rubella virus (Ruv), every suspected case must be properly identified and diagnosed. Since 2017, in Milan (Italy), a total of 978 measles and rubella suspected cases (fever and rash) were investigated and 310 were not laboratory confirmed (discarded cases). To improve surveillance activities, we investigated the presence in discarded cases of 8 other viral pathogens commonly associated with rash: human herpesvirus 6 (HHV-6) and 7 (HHV-7), parvovirus B19 (B19V), enterovirus (EV), Epstein-Barr virus (EBV), human adenovirus (HAdV), cytomegalovirus (HCMV), and SARS-CoV-2. Differential diagnosis was carried out on 289 discarded cases by multiplex real-time PCR assays. At least one pathogen was detected in 188 cases (65.1%) with HHV-7 being the most frequently detected virus. No difference in the number of detected infections overtime was observed and infections were identified in all age groups. As expected, most HHV-6, EV, HAdV, and HCMV-positive cases were found in children aged 0-4 years and HHV-7 was most frequent in the 15-39 age group. In light of the World Health Organization measles elimination goal, the introduction of laboratory methods for differential diagnosis is required for the final classification of clinically compatible cases. The used screening panel allowed us to increase the percentage of virus-positive cases to 87.5%, allowing us to clarify viral involvement and epidemiology, improve diagnosis, and strengthen surveillance activities. As all investigated pathogens were detected, this diagnostic panel was a suitable tool to complement MV and RuV surveillance activities.


Assuntos
Adenovírus Humanos , Infecções por Enterovirus , Enterovirus , Infecções por Vírus Epstein-Barr , Exantema , Herpesvirus Humano 6 , Sarampo , Rubéola (Sarampo Alemão) , Criança , Humanos , Adolescente , Adulto Jovem , Adulto , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/diagnóstico , Anticorpos Antivirais , Imunoglobulina M , Herpesvirus Humano 4 , Sarampo/diagnóstico , Sarampo/epidemiologia , Sarampo/prevenção & controle , Rubéola (Sarampo Alemão)/diagnóstico , Rubéola (Sarampo Alemão)/epidemiologia , Vírus do Sarampo/genética , Febre , Infecções por Enterovirus/diagnóstico , Herpesvirus Humano 6/genética
20.
J Virol ; 97(9): e0071823, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37671864

RESUMO

Nascent nucleocapsids of herpesviruses acquire a primary envelope during their nuclear export by budding through the inner nuclear membrane into the perinuclear space between the inner and outer nuclear membranes. This process is mediated by a conserved viral heterodimeric complex designated the nuclear egress complex, which consists of the nuclear matrix protein and the nuclear membrane protein. In addition to its essential roles during nuclear egress, the nuclear matrix protein has been shown to interact with intracellular signaling pathway molecules including NF-κB and IFN-ß to affect viral or cellular gene expression. The human herpesvirus 6A (HHV-6A) U37 gene encodes a nuclear matrix protein, the role of which has not been analyzed. Here, we show that HHV-6A U37 activates the heat shock element promoter and induces the accumulation of the molecular chaperone Hsp90. Mechanistically, HHV-6A U37 interacts with heat shock transcription factor 1 (HSF1) and induces its phosphorylation at Ser-326. We report that pharmacological inhibition of HSF1, Hsp70, or Hsp90 decreases viral protein accumulation and viral replication. Taken together, our results lead us to propose a model in which HHV-6A U37 activates the heat shock response to support viral gene expression and replication. IMPORTANCE Human herpesvirus 6A (HHV-6A) is a dsDNA virus belonging to the Roseolovirus genus within the Betaherpesvirinae subfamily. It is frequently found in patients with neuroinflammatory disease, although its pathogenetic role, if any, awaits elucidation. The heat shock response is important for cell survival under stressful conditions that disrupt homeostasis. Our results indicate that HHV-6A U37 activates the heat shock element promoter and leads to the accumulation of heat shock proteins. Next, we show that the heat shock response is important for viral replication. Overall, our findings provide new insights into the function of HHV-6A U37 in host cell signaling and identify potential cellular targets involved in HHV-6A pathogenesis and replication.


Assuntos
Fatores de Transcrição de Choque Térmico , Resposta ao Choque Térmico , Herpesvirus Humano 6 , Proteínas da Matriz Viral , Humanos , Fatores de Transcrição de Choque Térmico/metabolismo , Resposta ao Choque Térmico/genética , Herpesvirus Humano 6/metabolismo , Herpesvirus Humano 6/patogenicidade , Proteínas da Matriz Viral/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Regiões Promotoras Genéticas , Replicação Viral , Fosforilação , Regulação Viral da Expressão Gênica , Transdução de Sinais
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