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1.
J Virol Methods ; 311: 114640, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36332714

RESUMO

HBV cure rates remain low despite prolonged nucleos(t)ide (NrtI) therapy, likely due to persistent residual viral replication and an inability to eliminate covalently closed circular DNA (cccDNA). Therapies with novel mechanisms of action against hepatitis B virus (HBV) are being explored with the goal of achieving sustained off-treatment response and a functional cure without requiring lifelong therapy. Recent studies have indicated that serum HBV DNA levels (a biomarker for viral replication) combined with serum pregenomic RNA (pgRNA) levels (a surrogate for intrahepatic cccDNA transcriptional activity), may provide a better prediction for the risk of liver-related complications. Current HBV DNA assays, such as the COBAS AmpliPrep/COBAS TaqMan HBV test v2.0, quantitate HBV DNA down to 20 IU/mL, but are not able to monitor loss of residual virus in patients on NrtI therapy. There are no commercially available assays approved to detect serum/plasma HBV pgRNA levels. We have developed a multi-assay panel of highly sensitive nucleic acid assays designed to monitor levels of HBV DNA, pgRNA and total nucleic acids (TNA, composite DNA + pgRNA) in clinical specimens and to monitor changes during treatment with new antiviral combination regimens.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , DNA Viral/genética , Vírus da Hepatite B/genética , DNA Circular/genética , RNA , Antivirais/uso terapêutico
2.
Sci Total Environ ; 856(Pt 2): 159166, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36202364

RESUMO

Monkeypox disease (MPXD), a viral disease caused by the monkeypox virus (MPXV), is an emerging zoonotic disease endemic in some countries of Central and Western Africa but seldom reported outside the affected region. Since May 2022, MPXD has been reported at least in 74 countries globally, prompting the World Health Organization to declare the MPXD outbreak a Public Health Emergency of International Concern. As of July 24, 2022; 92 % (68/74) of the countries with reported MPXD cases had no historical MPXD case reports. From the One Health perspective, the spread of MPXV in the environment poses a risk not only to humans but also to small mammals and may, ultimately, spread to potent novel host populations. Wastewater-based surveillance (WBS) has been extensively utilized to monitor communicable diseases, particularly during the ongoing COVID-19 pandemic. It helped in monitoring infectious disease caseloads as well as specific viral variants circulating in communities. The detection of MPXV DNA in lesion materials (e.g. skin, vesicle fluid, crusts), skin rashes, and various body fluids, including respiratory and nasal secretions, saliva, urine, feces, and semen of infected individuals, supports the possibility of using WBS as an early proxy for the detection of MPXV infections. WBS of MPXV DNA can be used to monitor MPXV activity/trends in sewerage network areas even before detecting laboratory-confirmed clinical cases within a community. However, several factors affect the detection of MPXV in wastewater including, but not limited to, routes and duration time of virus shedding by infected individuals, infection rates in the relevant affected population, environmental persistence, the processes and analytical sensitivity of the used methods. Further research is needed to identify the key factors that impact the detection of MPXV biomarkers in wastewater and improve the utility of WBS of MPXV as an early warning and monitoring tool for safeguarding human health. In this review, we shortly summarize aspects of the MPXV outbreak relevant to wastewater monitoring and discuss the challenges associated with WBS.


Assuntos
COVID-19 , Varíola dos Macacos , Animais , Humanos , Varíola dos Macacos/epidemiologia , Varíola dos Macacos/diagnóstico , Varíola dos Macacos/patologia , Águas Residuárias , Pandemias , COVID-19/epidemiologia , Vírus da Varíola dos Macacos/genética , DNA Viral , Monitoramento Ambiental , Mamíferos
3.
J Ethnopharmacol ; 302(Pt A): 115896, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36334815

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza (the roots of S. miltiorrhiza Bunge, Danshen in Chinese), a traditional Chinese medicine, has been clinically used to prevent and treat various diseases, such as cardiovascular and cerebrovascular diseases, diabetes, and hepatitis B, in China and some other Asian countries. Lithospermic acid (LA), a polyphenol derived from S. miltiorrhiza, has been reported to exhibit multiple pharmacological properties, such as anti-inflammatory, anti-HIV, and anti-carbon tetrachloride-induced liver injury activities. However, little is known about the anti-hepatitis B virus (HBV) activity of LA. AIM OF THE STUDY: The study was projected to investigate the anti-HBV activity of LA in vitro (HepG2.2.15 and pHBV1.3-transfected HepG2 cells) and in vivo (pAAV-HBV1.2 hydrodynamic injection [HBV-HDI] mice) and explore the potential mechanism as well. MATERIALS AND METHODS: Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) contents were detected by ELISA kits. HBV DNA and hepatitis B core antigen (HBcAg) levels were evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry assay, respectively. The proteins in autophagy process, lysosomal acidic function, and autophagy-related signaling pathways were examined by Western blot. Transmission electron microscopy was used to observe the number of autophagosomes and autolysosomes. Confocal microscopy was applied to analyze the autophagic flux and lysosomal acidification, using mCherry-enhanced green fluorescent protein (EGFP)-microtubule-associated protein light chain (LC)3 and lysosomal probes, respectively. RESULTS: LA exhibited anti-HBV activity by inhibiting HBV DNA replication in HepG2.2.15 and pHBV-transfected HepG2 cells in dose- and time-dependent manners and hampering HBsAg and HBeAg levels in HepG2.2.15 cells to a certain extent. LA reduced HBV DNA, HBsAg/HBeAg, and HBcAg levels in the serum/liver tissues of HBV-HDI C57BL/6 mice during the 3-week treatment and suppressed the withdrawal rebound of HBV DNA and HBsAg in the mice serum. LA increased LC3-II protein expression and the number of autolysosomes/autophagosomes and promoted the degradation of sequestosome 1(p62) protein in vitro and in vivo. LA enhanced the co-localization of LC3 protein with autolysosomes, further confirming the ability of LA to induce a complete autophagy. Knockdown of autophagy-related gene (Atg) 7 or 5 in vitro and administration of 3-methyladenine (an autophagic inhibitor) in vivo disabled the inhibitory efficacy of LA on HBV DNA replication, suggesting that the anti-HBV efficacy of LA depended on its ability of inducing autophagy. LA could enhance lysosomal acidification and improve the function of lysosomes by promoting the protein expression of lysosomal-associated membrane protein (LAMP)-1, LAMP-2, and mature cathepsin D, which may contribute to the autophagic induction of LA. LA inhibited the activation of AKT and mammalian target of rapamycin (mTOR) induced by HBV, which was reversed by IGF-1 (an agonist of the PI3K/AKT/mTOR signaling pathway), indicating that LA elicited autophagy through hampering the PI3K/AKT/mTOR signaling pathway. CONCLUSION: We revealed the anti-HBV activity and mechanism of LA in vitro and in vivo. This study facilitates a new understanding of the anti-HBV potent components of S. miltiorrhiza and sheds light on LA for further development as an active constituent or candidate used in the therapy against HBV infection.


Assuntos
Hepatite B , Herpesvirus Cercopitecino 1 , Salvia miltiorrhiza , Camundongos , Animais , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B/genética , Antígenos do Núcleo do Vírus da Hepatite B/genética , Polifenóis/metabolismo , Herpesvirus Cercopitecino 1/genética , Herpesvirus Cercopitecino 1/metabolismo , Antígenos E da Hepatite B , DNA Viral/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Replicação Viral/fisiologia , Camundongos Endogâmicos C57BL , Autofagia , Serina-Treonina Quinases TOR/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
4.
BMC Infect Dis ; 22(1): 842, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368952

RESUMO

PURPOSE: This study was designed to analyze the liver tissue changes among the CHB patients who received treatment for at least 6 months and follow-up for at least 1 year, together with the correlation between the different disease condition and serum markers. METHODS: One-hundred and eighty-five CHB patients underwent antiviral therapy for at least 6 months were enrolled. In the 12-month follow-up, ultrasonography-guided biopsy was performed. The patients were grouped based on the serum markers and pathological changes in liver tissues. Then we determined the serum markers, virological tests and Tim-3 expression among these groups. RESULTS: Antiviral therapy significantly reduced liver inflammation indicators and serum Tim-3 level. However, the fibrosis process of liver tissue was not changed, and there are still disputes on the serum marker and hepatic lesion outcomes. Under normal liver function or negative hepatitis B e antigen (HBeAg) of CHB patients, there might be consensus between Tim-3 change and liver pathological outcome. According to the liver tissue inflammation and fibrosis conditions, Tim-3 was positively correlated with liver function indices. Besides, it was also related to fibrosis stage and inflammation grade. CONCLUSION: There were inconsistent changes between serum markers and liver tissue conditions after anti-viral therapy. Tim-3 expression was more suitable to indicate the changes of liver inflammatory and fibrosis response to some extent than ALT and AST. It may serve as a certain indicator to predict the CHB prognosis, which could be used as one of the monitoring indicators in liver pathological changes of chronic HBV infection, especially in monitoring liver tissue inflammation.


Assuntos
Vírus da Hepatite B , Hepatite B Crônica , Humanos , Vírus da Hepatite B/genética , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/uso terapêutico , Antígenos E da Hepatite B , Fígado/patologia , Prognóstico , Inflamação/tratamento farmacológico , Fibrose , Biomarcadores/metabolismo , Antivirais/uso terapêutico , DNA Viral , Alanina Transaminase
5.
J Infect Dev Ctries ; 16(10): 1630-1636, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36332217

RESUMO

INTRODUCTION: The most common infection in cholestatic infants is caused by human cytomegalovirus (HCMV). The aims were to detect the presentation of HCMV in cholestatic infants and to evaluate the concordance, sensitivity, and specificity between serology and polymerase chain reaction (PCR) of HCMV from liver biopsy and urine specimens. METHODOLOGY: A descriptive observational study with a cross-sectional approach was conducted on 35 cholestatic infants with ethical approval. Specimens were liver biopsy, urine, and anti-HCMV serology. Liver and urine specimens were performed to nested PCR, followed by statistical analysis. RESULTS: PCR from the liver biopsy and urine specimen were positive in 74.3% and 85.7%, respectively. There was no concordance between IgM with the liver PCR, but there was a concordance between IgM with the urine PCR and between IgG with the liver and urine PCR. The sensitivity and specificity of IgM with the liver PCR were 46 % and 56%, respectively, with a diagnostic accuracy of 49%. While IgG sensitivity was 96% with a diagnostic accuracy of 80%. IgG sensitivity and IgM specificity compared with the urine PCR were 93% and 100%, respectively, with a diagnostic accuracy of more than 60%. CONCLUSIONS: It demonstrates a high prevalence of HCMV DNA in urine and liver biopsy from cholestatic infants. HCMV PCR assay is more sensitive and specific than the anti-HCMV IgM, but IgG has high sensitivity and accuracy diagnostic. Therefore, serological examination is an option for diagnosing HCMV infection in cholestatic infants in developing countries with no PCR facilities.


Assuntos
Colestase , Infecções por Citomegalovirus , Lactente , Humanos , Citomegalovirus/genética , Infecções por Citomegalovirus/diagnóstico , DNA Viral/genética , Reação em Cadeia da Polimerase , Colestase/diagnóstico , Colestase/patologia , Fígado/patologia , Testes Sorológicos , Imunoglobulina M , Imunoglobulina G
6.
Front Public Health ; 10: 1037508, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388269

RESUMO

Background and aim: Chronic hepatitis B (CHB) can be divided into immune tolerance (IT), immune clearance (IC), hepatitis B e antigen (HBeAg)-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. The conventional biomarkers used to distinguish these phases have limitations. We examined the clinical significance of hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) as novel biomarkers. Methods: One hundred eighty-nine patients without treatment currently were categorized by CHB phase (IT = 46, IC = 45, ENQ = 49, ENH = 49). The associations of HBV RNA and HBcrAg with HBV DNA and alanine transaminase (ALT) were analyzed. The decision tree model was used to distinguish the four phases in the natural course of CHB. Results: The concentrations of HBV RNA and HBcrAg were highest in the IT and IC phases (P < 0.01). Serum HBV RNA was similar to HBcrAg in treatment-naïve patients. HBV RNA and HBcrAg correlated with HBV DNA in the HBeAg+ and HBeAg- status (HBV RNA: e+ r = 0.51, e- r = 0.62; HBcrAg: e+ r = 0.51, e- r = 0.71), but their association with HBV DNA differed among phases. The accuracy, sensitivity, and specificity of HBcrAg with ALT in distinguishing the CHB phases were 95.65%, 95.83%, and 95.55%, respectively. Conclusion: Serum HBV RNA and HBcrAg may be useful to monitor CHB progression.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Antígenos E da Hepatite B/uso terapêutico , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , DNA Viral/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/uso terapêutico , Biomarcadores , RNA/uso terapêutico
7.
Antivir Ther ; 27(6): 13596535221127848, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36382358

RESUMO

BACKGROUND: Chronic hepatitis B (CHB) remains a major cause of morbidity and mortality. EDP-514 is a potent core inhibitor of hepatitis B virus (HBV) that reduces viral load reduction in HBV-infected chimeric mice. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics (PK) of EDP-514 in healthy subjects and antiviral activity in patients with CHB. METHODS: In Part 1, 82 subjects received placebo or EDP-514 in fed or fasted state as single ascending doses of 50-800 mg and multiple ascending doses of 200-800 mg for 14 days. In Part 2, 24 HBV DNA-suppressed, nucleos(t)ide (NUC)-treated (i.e., NUC-suppressed) CHB patients received EDP-514 200-800 mg or placebo for 28 days. RESULTS: EDP-514 was well tolerated in healthy subjects and CHB patients with most adverse events of mild intensity. In Part 1, EDP-514 exposure increased in an approximately dose proportional manner up to 600 mg after single doses and up to 400 mg after 14-day dosing. In Part 2, EDP-514 exposure increased linearly with dose on Day 1 and Day 28, with some accumulation for Day 28 and median trough concentrations (Ctrough) approximately 20-fold above the protein-adjusted 50% effective concentration (EC50) for the dose range. Mean change in HBV RNA from baseline to Day 28 was -2.03, -1.67, -1.87, and -0.58 log U/mL in the 200 mg, 400 mg, 800 mg, and placebo CHB groups, respectively. CONCLUSIONS: EDP-514 was well tolerated, had a PK profile supporting once daily dosing, and reduced HBV RNA levels in NUC-suppressed CHB patients.


Assuntos
Hepatite B Crônica , Humanos , Camundongos , Animais , Hepatite B Crônica/tratamento farmacológico , Inibidores da Transcriptase Reversa/efeitos adversos , Voluntários Saudáveis , Vírus da Hepatite B/genética , Antivirais/efeitos adversos , RNA/farmacologia , RNA/uso terapêutico , Antígenos E da Hepatite B , DNA Viral/genética
8.
BMC Infect Dis ; 22(1): 863, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401190

RESUMO

BACKGROUND: The long-term protective effect of hepatitis B vaccine (HepB), the incidence of hepatitis B virus (HBV) vaccine breakthrough infections (VBIs), and whether a booster HepB is necessary remain to be clarified in children born to mothers with chronic HBV infection. METHODS: Based on a long-term follow-up prospective cohort of 1177 hepatitis B surface antigen (HBsAg)-positive mothers and their paired infants which was established from 2009 to 2011, total 454 children with immunoprophylaxis success as determined by postvaccination serologic testing (PVST) at 7 months old were included in this study. Among the 454 children, 246 never had a booster HepB, and 208 children received a booster HepB from 1 to 5 years of age. Multivariate logistic regression analysis was used to analyse the risk factors for HBV VBIs. RESULTS: The hepatitis B surface antibody (anti-HBs) levels declined sharply from 7 months to 2 years old, and the anti-HBs seronegative rate in the children increased significantly from 2 years old. A total of 31 (6.83%) of the 454 children experienced VBIs, of which 7 had overt and 7 had occult HBV infections. Notably, 14 (45.16%) of the 31 children with VBIs were diagnosed at 2 years old, and all of them had anti-HBs positivity (> 10 mIU/mL) at 1 year old. Maternal hepatitis B e antigen (HBeAg) positivity, higher HBV DNA and HBsAg levels, lower initial infant anti-HBs levels and not receiving a booster HepB were independent risk factors for VBIs. The incidence of VBIs was significantly lower in children with a booster HepB than in nonboosted children (0.50 vs. 11.90%, P < 0.001), and none of the boosted children developed overt or occult HBV infection. The anti-HBs levels of 76.67% for the children with VBIs in the nonboosted group indicated positivity before VBIs was detected. CONCLUSIONS: After the primary full immunization with HepB, children born to mothers with chronic HBV infection, especially the children with maternal HBeAg positivity, high HBV DNA levels, high HBsAg levels and/or low initial infant anti-HBs levels, were at a high risk of VBIs, and a booster HepB for these children before 2 years old, instead of when their anti-HBs level is < 10 mIU/mL, could reduce the incidence of VBIs.


Assuntos
Vacinas contra Hepatite B , Hepatite B Crônica , Humanos , Criança , Lactente , Pré-Escolar , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , DNA Viral , Estudos Prospectivos , Anticorpos Anti-Hepatite B , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico
9.
BMJ Open ; 12(11): e063482, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36351715

RESUMO

OBJECTIVES: Eliminating mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is central to WHO's target of reducing hepatitis B infection in children to <0.1% by 2030. While Nigeria accounts for 8.3% of the global burden, interventional studies on prevention of MTCT of HBV are hardly available. This study aimed to assess the impact of prevention of MTCT interventions on vertical transmission of HBV among pregnant women in Nigeria. DESIGN: A prospective cohort study. SETTING: A University Teaching Hospitals Complex in Nigeria between 2015 and 2021. PARTICIPANTS: 10 866 pregnant women and their pre-existing children. INTERVENTIONS: Eligible pregnant women were screened for HBsAg using chromatographic immunoassay (Micropoint, USA). HbsAg-positive women had HBV serological assay done and their pre-existing children were screened. Women with HBV DNA ≥2 00 000 IU/mL and those positive for hepatitis B e-antigen (HBeAg) had 300 mg/day of Tenofovir Disoproxil Fumarate (TDF) in the third trimester. The newborns had hepatitis B vaccines and HB immunoglobulin (HBIG) administered, followed by testing for HBsAg at 9 months postnatally. PRIMARY OUTCOME MEASURES: Prevalence of chronic hepatitis B infection in pregnancy, and the incidence of MTCT of HBV. RESULTS: Overall, 395 women had chronic HBV infection, giving a prevalence of 3.64%. Their mean age was 31.51±5.71 years, with a median parity of 1.2. Thirteen women (5.2%) were positive for HBeAg, seven (3.1%) of the 225 pre-existing hepatitis B-exposed children were HbsAg positive and 17 women had prenatal TDF. Overall, 376 women completed the study, with mean birth weight of 3.21±1.86 kg and perinatal mortality rate of 29.2/1000 births. Hepatitis Bvaccine-HBIG combination was administered to 260 newborns, while the others had hepatitis B vaccine alone. All the children tested negative to the HbsAg at 9 months. CONCLUSION: Eliminating MTCT of HBV infection through validated protocols in low and middle income countries with the highest burden of chronic HBV infections is feasible. National scale-up of such protocols is recommended.


Assuntos
Hepatite B Crônica , Hepatite B , Complicações Infecciosas na Gravidez , Lactente , Feminino , Recém-Nascido , Gravidez , Humanos , Adulto , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Antígenos E da Hepatite B , Antígenos de Superfície da Hepatite B , Estudos Prospectivos , Seguimentos , Nigéria/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , DNA Viral , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vírus da Hepatite B , Vacinas contra Hepatite B/uso terapêutico , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Tenofovir/uso terapêutico , Imunoglobulinas/uso terapêutico
10.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(11): 1642-1647, 2022 Nov 06.
Artigo em Chinês | MEDLINE | ID: mdl-36372757

RESUMO

To investigate the correlation between serum cytomegalovirus (CMV) IgM antibody/viral load and infection-related clinical symptoms in neonates infected with CMV, and provide basis for clinical assessment and monitoring of neonatal CMV infection. A total of 70 neonates with CMV infection admitted to neonatology in Women's Hospital, School of Medicine Zhejiang University, from January 2014 to December 2020 were included in this study. Using real-time quantitative PCR as the diagnostic criteria, congenital cytomegalovirus-infected neonates (n=29) was diagnosed within the first 3 weeks of life, otherwise, it was postnatally acquired cytomegalovirus infection (n=41). The differences in general information and clinical indicators between IgM antibody positive and negative patients were analyzed, combined with the PCR result, the correlation between the IgM/viral load and the occurrence of symptoms were analyzed. T-test and non-parametric test were used to compare the differences of indicators between groups, logistic regression was used for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of relevant indicators. In the congenital CMV infection group and the postnatally acquired CMV infection group, viral load and the proportion of symptomatic patients in IgM positive group were significantly higher than IgM negative group (Z=-2.616, P=0.008; 80% vs. 21%, P=0.005) (Z=-2.405, P=0.016; 56% vs. 19%, P=0.025). Logistic regression analysis of the included population showed the risk factors of CMV infection-related symptoms were IgM positive (OR 4.562, 95%CI:1.461-14.246,P=0.009) and viral load (OR 1.728, 95%CI:1.068-2.798,P=0.026). Regressive analysis for single symptom with correction showed IgM antibody positive was associated with hearing dysfunction(OR 3.954, 95%CI:1.066-14.677,P=0.040),the CMV viral load was associated with thrombocytopenia (OR 2.228, 95%CI:1.124-4.413,P=0.022), and brain imaging abnormalities (OR 3.956, 95%CI:1.421-11.011, P=0.008). Receiver operating characteristic (ROC) analysis showed the area under ROC curve of CMV viral load for brain imaging abnormalities was 0.883 (P<0.001), with a sensitivity of 75.0% and specificity of 90.3%. For neonates infected with CMV, the risk of infection-related clinical symptoms and hearing dysfunction may be increased when IgM antibody was positive. Meanwhile, the higher the CMV viral load at diagnosis, the higher the risk of thrombocytopenia and abnormal brain imaging.


Assuntos
Infecções por Citomegalovirus , Trombocitopenia , Recém-Nascido , Humanos , Feminino , Citomegalovirus/genética , Imunoglobulina M , Carga Viral , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Anticorpos Antivirais , Reação em Cadeia da Polimerase em Tempo Real , Trombocitopenia/complicações , DNA Viral
11.
Cancer Control ; 29: 10732748221140785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36377557

RESUMO

BACKGROUND: In vitro studies have produced conflicting results about the significance of the JC Polyoma Virus (JCV) in the human cancers. OBJECTIVES: Our study aims to detect the presence of JCV Large T antigen (LTag) together with viral load quantitation in the prostate tumor samples to assess if JCV harbors risk factor for prostate cancer (PCa). METHOD: This was a case control-based study. A total of 110 patients participated in this study, including 55 patients with PCa and another 55 patients with benign prostatic hyperplasia (BPH) as cases and controls, respectively. Tissue, blood and urine samples were collected from each participant. Tissues samples were analyzed for the presence of JCV Ltag using a direct immunofluorescence assay (IF). Only positive IF tested samples were subjected to viral quantitation assay. Data were collected and managed using SPSS version 20. RESULT: The JCV LTag in the cases group was 23.63% (13/55) which was higher than that of the controls group 5.45% (3/55) with a P. value of .006 and O.R of 5.76. The mean of viral load was significantly higher among cases tissue specimens 20156 ± 5450 copies/ml compared to controls group 6378 ± 2456copies/ml with P-value of .002. The virus was detected in 11/13 (84.6%) urine samples of cases with a mean viral load of 14068 ± 4590 copies/ml compared to 2/3 (66.6%) of controls viral load 2534 ± 1267 copies/ml. CONCLUSION: In conclusion, a higher JCV LTag with more viral load were detected in cases group compared to controls. Our findings support a strong relationship between JCV infection and the probability of developing PCa.


Assuntos
Vírus JC , Neoplasias da Próstata , Masculino , Humanos , Vírus JC/genética , Estudos de Casos e Controles , DNA Viral , Fatores de Risco , Imunofluorescência
12.
BMC Cancer ; 22(1): 1146, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344942

RESUMO

BACKGROUND: HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) are sensitive to chemo-radiation therapy and have favorable survival outcomes compared with HPV-negative cancers. These tumors are usually not related to tobacco and alcohol exposure. Therefore, diagnosing HPV-positive OPSCCs for the appropriate disease management is crucial, and no suitable markers are available for detecting early malignancies in HPV-infected tissues. In this study, we attempt to find HPV-specific epigenetic biomarkers for OPSCCs. METHODS: A total of 127 surgical samples were analyzed for HPV positivity and promoter methylation of a panel of genes. HPV detection was performed by PCR detection of HPV E6 and E7 viral oncoproteins. In addition, promoter methylation of a total of 8 genes (DAPK, FHIT, RASSF1A, TIMP3, AGTR1, CSGALNACT2, GULP1 and VGF) was analyzed by quantitative-methylation specific PCR (QMSP), and their associations with HPV positivity or RB/p16 expressions were evaluated. RESULTS: AGTR1 and FHIT were frequently methylated in HPV-positive OPSCC samples with a good area under the curve (AUC over 0.70). In addition, these genes' promoter methylation was significantly associated with p16 positive and RB negative cases, which were the characteristics of OPSCC cases with favorable survival outcomes. Either AGTR1 or FHIT methylated cases were significantly associated with HPV-positive cancers with 92.0% sensitivity (P < 0.001). Also, they had significantly better overall survival (P = 0.047) than both unmethylated cases. CONCLUSIONS: A combination of AGTR1 and FHIT methylation demonstrated a suitable detection marker of OPSCCs derived from the HPV-infected field, familiar with p16-positive and RB-negative phenotypes.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Proteínas Oncogênicas Virais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas/patologia , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/metabolismo , Neoplasias de Cabeça e Pescoço/complicações , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Papillomaviridae/genética , Papillomaviridae/metabolismo , DNA Viral/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
13.
BMC Gastroenterol ; 22(1): 452, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352372

RESUMO

BACKGROUND AND AIMS: Patients with low HBV DNA levels (< 2000 IU/mL), HBV DNA negative, and HBsAg-negative hepatitis B virus(HBV)infection can still progress to decompensated cirrhosis; however, clinical research data in such patients, especially treatment-naïve patients, are currently insufficient. This study assessed the natural history of aforementioned patients. METHODS: We retrospectively reviewed the data of 250 patients with HBV-associated decompensated cirrhosis(HBV DNA < 2000 IU/mL) who had not been treated with antiviral medication. RESULTS: The mean age of the 250 patients was 53.90 ± 11.73 years and 183 patients (73.2%) were male. HBV DNA, HBsAg, and HBeAg positivity was detected in 77 (30.8%), 200 (80%), and 137 (54.8%) patients, respectively. HBsAg (odds ratio [OR], 3.303; 95% confidence interval [CI], 1.338-8.152; P = 0.010) and HBeAg (OR, 0.200; 95% CI, 0.107-0.376; P < 0.001) positivity were independent factors for low HBV DNA levels. The incidence of hepatocellular carcinoma (HCC) (P < 0.001) and portal vein thrombosis (P = 0.001) was higher in the low HBV DNA levels group. Multivariate analysis showed that HBV DNA positivity (OR, 3.548; 95% CI, 1.463-8.604; P = 0.005), HBeAg positivity (OR, 0.080; 95% CI, 0.022-0.289; P < 0.001), and glutamyltransferase (GGT) (OR, 1.003; 95% CI, 1.000-1.006; P = 0.040) were independent factors for HCC. Age was not related to the occurrence of cirrhosis complications. CONCLUSION: Patients with decompensated cirrhosis with HBV DNA < 2000 IU/mL still had severe liver damage and could develop severe cirrhosis complications. HCC risk was higher in low HBV DNA levels patients. HBsAg positivity and HBeAg negativity may be associated to the occurrence of low HBV DNA levels.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Antígenos E da Hepatite B , Antígenos de Superfície da Hepatite B , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/complicações , Estudos Retrospectivos , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , DNA Viral , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/complicações , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Vírus da Hepatite B/genética , Cirrose Hepática/complicações
14.
Microb Genom ; 8(11)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36355418

RESUMO

Whole-genome sequencing is widely used to better understand the transmission dynamics, the evolution and the emergence of new variants of viral pathogens. This can bring crucial information to stakeholders for disease management. Unfortunately, aquatic virus genomes are usually difficult to characterize because most of these viruses cannot be easily propagated in vitro. Developing methodologies for routine genome sequencing of aquatic viruses is timely given the ongoing threat of disease emergence. This is particularly true for pathogenic viruses infecting species of commercial interest that are widely exchanged between production basins or countries. For example, the ostreid herpesvirus type 1 (OsHV-1) is a Herpesvirus widely associated with mass mortality events of juvenile Pacific oyster Crassostrea gigas. Genomes of Herpesviruses are large and complex with long direct and inverted terminal repeats. In addition, OsHV-1 is unculturable. It therefore accumulates several features that make its genome sequencing and assembly challenging. To overcome these difficulties, we developed a tangential flow filtration (TFF) method to enrich OsHV-1 infective particles from infected host tissues. This virus purification allowed us to extract high molecular weight and high-quality viral DNA that was subjected to Illumina short-read and Nanopore long-read sequencing. Dedicated bioinformatic pipelines were developed to assemble complete OsHV-1 genomes with reads from both sequencing technologies. Nanopore sequencing allowed characterization of new structural variations and major viral isomers while having 99,98 % of nucleotide identity with the Illumina assembled genome. Our study shows that TFF-based purification method, coupled with Nanopore sequencing, is a promising approach to enable in field sequencing of unculturable aquatic DNA virus.


Assuntos
Crassostrea , Vírus de DNA , Herpesviridae , Animais , Crassostrea/genética , Vírus de DNA/genética , DNA Viral/genética , Herpesviridae/genética
15.
Front Immunol ; 13: 1036612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353632

RESUMO

Objective: We explore the expression of functional molecules on CD8+ T lymphocytes, cytokines concentration, and their correlation to occurrence of hepatitis B and hepatitis B virus (HBV) desoxyribose nucleic acid (DNA), hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), and alanine aminotransferase (ALT) in patients infected with HBV. Methods: This is a single center study. 32 patients with acute hepatitis B (AHB), 30 patients with immune tolerant (IT) phase chronic HBV infected, and 50 patients with chronic hepatitis B (CHB) were enrolled. The activation molecules (CD69) and the apoptosis-inducing molecules (CD178) on surface of CD8+ T lymphocytes were tested by the flow cytometry. Fms-like tyrosine kinase 3 ligand (Flt-3L), interleukin 17A (IL-17A), interferon γ (IFN-γ), and Interferon α2 (IFN-α2) were quantitated by Luminex assay. We use linear regression analysis to analyze their correlations to ALT, HBV DNA, HBsAg, and HBeAg. Results: The frequency of CD69+CD8+ T lymphocytes in CHB and AHB groups were increased significantly compared with IT group (4.19[3.01, 6.18]% and 4.45[2.93, 6.71]% vs. 3.02[2.17, 3.44]%; H=26.207, P=0.001; H=28.585, P=0.002), and the mean fluorescence intensity (MFI) of CD69 in AHB group was significantly higher than IT and CHB groups (27.35[24.88, 32.25] vs. 20.45[19.05, 27.75] and 23.40[16.78, 28.13]; H=25.832, P=0.005 and H=22.056, P=0.008). In IT group, HBsAg levels and HBV DNA loads were negatively correlated with CD69MFI (ß=-0.025, t=-2.613, P=0.014; ß=-0.021, t=-2.286, P=0.030), meanwhile, HBeAg was negatively related to the frequency of CD69+CD8+ T lymphocytes (ß=-61.306, t=-2.116, P=0.043). In AHB group, IFN-α2 was positively related to the frequency of CD8+ T lymphocytes (ß=6.798, t=2.629, P=0.016); however, in CHB group, IFN-α2 was negatively associated with frequency of CD8+ T lymphocytes (ß=-14.534, t=-2.085, P=0.043). In CHB group, HBeAg was positively associated with frequency of CD69+CD8+ T lymphocytes (ß=43.912, t=2.027, P=0.048). In AHB group, ALT was positively related to CD69MFI (ß=35.042, t=2.896, P=0.007), but HBsAg was negatively related to CD178MFI (ß=-0.137, t=-3.273, P=0.003). Conclusions: The activation of CD8+ T lymphocytes was associated with the occurrence of AHB and CHB. However, due to the insufficient expression of functional molecules of CD8+ T lymphocytes and the depletion of CD8+ T lymphocytes, CHB patients were difficult to recover from HBV infection.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B , DNA Viral/metabolismo , Vírus da Hepatite B , Linfócitos T CD8-Positivos/metabolismo , Citocinas/metabolismo
16.
BMC Cancer ; 22(1): 1129, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329397

RESUMO

PURPOSE: To analyze the clinical outcomes of patients with regional persistent/recurrent nasopharyngeal carcinoma (NPC) who received neck dissection, and to evaluate the clinical benefit of postoperative adjuvant therapy (PAT) based on patients' positive lymph node counts (PLNs), extracapsular spread (ECS) and preoperative plasma EBV DNA levels. METHODS: From 2003 to 2017, 342 patients with regional persistent/recurrent NPC were included in this study. All patients were treated with neck dissection and 76 patients received PAT. Progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were compared between groups using propensity score matching (PSM). RESULTS: 152 patients without PAT treatment and 76 patients with PAT treatment were selected by the PSM. There was no significant difference in 2-year PFS (52.4% vs. 61.3%, P = 0.371), 2-year OS (91.9% vs. 90.5%, P = 0.097) or 2-year LRFS (66.3% vs. 67.9%, P = 0.872) between the two groups. However, the application of PAT brought survival benefits to patients in terms of 2-year DMFS (76.5% vs. 84.7%, P = 0.020). PLN, ECS and preoperative EBV DNA level remained independent risk factors for poorer PFS. Accordingly, patients were divided into low-risk and high-risk groups using receiver operating characteristic (ROC) curve; the 2-year PFS rates for two risk groups were 73.4% and 59.1% (P < 0.0001) respectively. The results showed that low-risk patients didn't benefit from the addition of PAT. However, the 2-year DMFS rate was significantly improved in high-risk PAT-treated patients than those treated by neck dissection alone (83.7% vs. 71.7%, P = 0.023). CONCLUSIONS: PLNs, ECS and preoperative EBV DNA level are associated with the prognosis of patients with regional persistent/recurrent NPC. High-risk patients identified by PLNs, ECS and preoperative EBV DNA level may benefit from the addition of PAT after neck dissection.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/cirurgia , Esvaziamento Cervical , Herpesvirus Humano 4/genética , DNA Viral , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos
17.
Front Immunol ; 13: 1018053, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325353

RESUMO

Human hepatitis B virus (HBV) is a small, enveloped DNA virus that causes acute and chronic hepatitis. Chronic hepatitis B (CHB) is associated with hepatocellular carcinoma pathogenesis. Interferons (IFNs) have been used for the treatment of CHB for a long time, with advantages including less treatment duration and sustained virological response. Presently, various evidence suggests that epigenetic modification of the viral covalently closed circular DNA (cccDNA) and the host genome is crucial for the regulation of viral activity. This modification includes histone acetylation, DNA methylation, N6-methyladenosine, and non-coding RNA modification. IFN treatment for CHB can stimulate multiple IFN-stimulated genes for inhibiting virus replication. IFNs can also affect the HBV life cycle through epigenetic modulation. In this review, we summarized the different mechanisms through which IFN-α inhibits HBV replication, including epigenetic regulation. Moreover, the mechanisms underlying IFN activity are discussed, which indicated its potential as a novel treatment for CHB. It is proposed that epigenetic changes such as histone acetylation, DNA methylation, m6A methylation could be the targets of IFN, which may offer a novel approach to HBV treatment.


Assuntos
Vírus da Hepatite B , Hepatite B , Humanos , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Epigênese Genética , Histonas/metabolismo , Hepatite B/tratamento farmacológico , Hepatite B/genética , Antivirais/uso terapêutico , Antivirais/farmacologia , DNA Viral/genética , Interferon-alfa/metabolismo
18.
Euro Surveill ; 27(45)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36367010

RESUMO

Before the international spread of monkeypox in May 2022, PCR kits for the detection of orthopoxviruses, and specifically monkeypox virus, were rarely available. Here we describe the evaluation of 11 recently developed commercially available PCR kits for the detection of monkeypox virus DNA. All tested kits are currently intended for research use only and clinical performance still needs to be assessed in more detail, but all were suitable for diagnostics of monkeypox virus, with variations in specificity rather than sensitivity.


Assuntos
Varíola dos Macacos , Humanos , Varíola dos Macacos/diagnóstico , Varíola dos Macacos/epidemiologia , Vírus da Varíola dos Macacos/genética , Berlim , DNA Viral/genética , DNA Viral/análise , Reação em Cadeia da Polimerase
19.
Oral Oncol ; 135: 106229, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36347145

RESUMO

OBJECTIVES: Plasma Epstein-Barr Virus (EBV)-DNA is a well-established prognostic biomarker in nasopharyngeal carcinoma (NPC). Different methods for assessment include single-copy gene targeted, European Conformity (CE)-marked assays, which are mostly employed in non-endemic settings, vs multiple-copy gene targeted, in-house BamHI-W based assays, which currently represent the most widely used method for EBV-DNA quantification. To date, evidence concerning the commutability of these different assays is still limited. MATERIALS AND METHODS: From August 2016 to March 2018, 124 plasma and 124 whole blood (WB) samples from 93 NPC patients were collected at different time-points for each patient. EBV-DNA viral load was quantified in pre- (n = 12) and post-treatment (n = 9), follow-up (n = 53), and recurrent/metastatic (R/M) (n = 50) phase. For each sample, one in-house BamHI-W vs three different CE-marked plasma assays were compared; the performance of plasma vs WB matrix was also assessed. Quantitative agreement of EBV-DNA values was evaluated by linear correlation and Bland-Altman analysis. RESULTS: A statistically significant (p = 0.0001) agreement between all CE-marked and the BamHI-W assays was found using plasma matrix, regardless of clinical phase. The results obtained in copies/ml were comparable to those expressed in IU/ml. When using WB matrix, the number of positive detections increased in the post-treatment phase. CONCLUSIONS: Our retrospective comparison supported an agreement between Plasma BamHI-W and CE-marked assays in measuring EBV-DNA for non-endemic NPC patients. There were no significant interferences from different measurement units (IU/ml vs copies/ml). Further evaluations are needed to better clarify the role of WB.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Estudos Retrospectivos , DNA Viral
20.
Viruses ; 14(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36366448

RESUMO

The extent to which perinatally HIV-infected children, following cART initiation, develop a low proviral reservoir burden over time, as measured by HIV DNA droplet-digital polymerase chain reaction (ddPCR) and the effect on HIV antibody is not well characterized. We measured proviral HIV DNA and plasma RNA virus load (VL) in 37 perinatally HIV-infected children at 6 months of age who initiated stable cART. At 6-11 years of age, HIV proviral DNA, HIV VL (RNA), and HIV antibody by Western Blot (WB) were assessed. CART was initiated before 6 months of age in 13 children and after 6 months in 24. At school age, the HIV DNA levels did not differ by the timing of cART, and the HIV DNA levels were lower in children with negative/indeterminate WB (p = 0.0256). Children with undetectable HIV RNA VL > 50% of the time since cART initiation had lower median DNA VL than children with undetectable VL < 50% of the time (p = 0.07). Long-term viral suppression in perinatally HIV-infected children is associated with a decrease in HIV antibodies and reduced HIV reservoirs.


Assuntos
Infecções por HIV , HIV-1 , Criança , Humanos , Lactente , Provírus/genética , Anticorpos Anti-HIV , HIV-1/genética , Carga Viral , Infecções por HIV/tratamento farmacológico , DNA Viral/análise , RNA
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