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1.
Chem Commun (Camb) ; 57(9): 1125-1128, 2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33410447

RESUMEN

Two fragments of the COVID-19 genome (specific and homologous) were used as two inputs to construct an AND logic gate for COVID-19 detection based on exonuclease III and DNAzyme. The detection sensitivity of the assay can reach fM levels. Satisfactory recovery values were obtained in real sample analysis.


Asunto(s)
/diagnóstico , ADN Viral/análisis , Saliva/virología , ADN Catalítico , ADN Viral/sangre , ADN Viral/orina , Exodesoxirribonucleasas , Genoma Viral , Humanos , Lógica
3.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33370940

RESUMEN

A 17-year-old Caucasian male presented to ENT with angular stomatitis, oral ulceration and cervical lymphadenopathy. Over the subsequent 18 months he developed recurrent upper respiratory tract infections, pyrexia of unknown origin, oral ulceration and maxillary sinus osteomyelitis. Extensive investigation ensued from various specialties. Positive investigations included a mild but persistently elevated serum Epstein-Barr virus PCR; however, no unifying diagnosis was elicited. It is noteworthy that a significant factor contributing to a delay in his diagnosis was poor compliance with invasive investigations. Ultimately, deteriorating liver function prompted liver biopsy which confirmed a diagnosis of chronic active Epstein-Barr virus infection (CAEBV). This enabled referral for curative treatment in the form of a stem cell transplant. CAEBV is extremely rare in Western countries. Due to fatal complications early diagnosis is critical for successful treatment. Our case highlights the need for regular clinical re-evaluation and a comprehensive multispecialty approach in such cases.


Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/aislamiento & purificación , Hígado/patología , Grupo de Atención al Paciente , Adolescente , Biopsia , Enfermedad Crónica/terapia , ADN Viral/sangre , ADN Viral/aislamiento & purificación , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/terapia , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/genética , Humanos , Hígado/virología , Pruebas de Función Hepática , Masculino , Derivación y Consulta , Trasplante de Células Madre
4.
BMJ ; 370: m2200, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32873599

RESUMEN

Hepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.


Asunto(s)
Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/virología , Replicación Viral/inmunología , Animales , ADN Viral/sangre , Salud Global , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Humanos , Inmunosupresión , Inmunosupresores/uso terapéutico , Factores de Riesgo
5.
Zhonghua Gan Zang Bing Za Zhi ; 28(7): 580-585, 2020 Jul 20.
Artículo en Chino | MEDLINE | ID: mdl-32791793

RESUMEN

Objective: To observe the alteration of clinical features of intrahepatic lymphocyte subsets in C57BL/6N-TG (1.28HBV)/Vst hepatitis B virus (HBV) transgenic mice composite carbon tetrachloride (CCl(4)) with intraperitoneal injection under the background of hepatitis B to induce liver fibrosis mice model, and analyze their correlation with serum HBV DNA and liver tissue hydroxyproline (Hyp) content. Methods: HBV-Tg mice were intraperitoneally injected with 10% CCl(4) to induce the rapid formation of hepatic fibrosis. Serum HBV DNA, HBsAg, HBeAg levels and liver tissue HBsAg expressional conditions were used to evaluate the virological characteristics of mice model. The degree of hepatic inflammation and fibrosis in mice were observed by HE, Sirius Red staining and liver tissue hydroxyproline (Hyp) content. Intrahepatic T lymphocyte, B lymphocyte, CD4+T lymphocyte, CD8+T lymphocyte, natural killer (NK) cell and natural killer T (NKT) cells distribution were observed by flow cytometry. One-way analysis of variance was used for intergroup data comparison, and LSD was used for pairwise comparison. Pearson's correlation analysis was used to analyze the correlation between the above lymphocyte subsets and serum HBV DNA and liver tissue Hyp content. Results: Serum HBsAg, HBeAg and liver tissue HBsAg had equal positive expression in the HBV-Tg composite CCl(4) mice model group, and the serum HBV DNA load was > 1 × 10(6) IU / ml. Compared with the wild-type control group, liver tissue Hyp content of the composite model group was significantly higher [(196.39 ± 38.14) µg /g and (347.67 ± 59.53) µ g/g, P < 0.01). The degree of inflammation and fibrosis in liver tissues was aggravated, and the proportion of all intrahepatic CD4+T, NK and NKT cells was significantly reduced (P < 0.01), while the proportion of CD8+T lymphocytes (30.58% ± 2.89% vs. 46.50% ± 2.24%, P < 0.01) and B lymphocytes (28.82% ± 2.24% vs. 37.10% ± 8.59%, P < 0.05) was significantly increased. Serum HBV DNA level was positively correlated with the proportion of intrahepatic T lymphocytes (r = 0.413, P < 0.05), and negatively correlated with the proportion of NK cells (r = -0.419, P < 0.05). Liver tissue Hyp content was negatively correlated with the proportion of all CD4+T lymphocytes (r = -0.871), NK cells (r = -0.716), and NKT cells (r = -0.876) (all P < 0.01), and positively correlated with the proportion of all CD8 + T lymphocytes (r = 0.852), and B lymphocytes (r = 0.593) (all P < 0.01). Conclusion: HBV-Tg composite CCl4 mice model can induce positive HBV virological indicators, liver inflammation and fibrosis in mice model of hepatitis B coexisting with fibrosis. This model has the features of immune disorder of liver lymphocyte similar to human disease, and the immune disorder of intrahepatic lymphocytes is correlated with HBV viral load and liver fibrosis degree.


Asunto(s)
Hepatitis B Crónica , Cirrosis Hepática/virología , Subgrupos Linfocitarios/citología , Animales , ADN Viral/sangre , Modelos Animales de Enfermedad , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/patología , Hidroxiprolina/análisis , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Ratones , Ratones Endogámicos C57BL
6.
PLoS One ; 15(8): e0238062, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32841308

RESUMEN

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7-14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management.


Asunto(s)
Citomegalovirus/genética , ADN Viral/sangre , Herpesvirus Humano 4/genética , Trasplante de Riñón , Adulto , Antivirales/farmacología , Estudios de Cohortes , Citomegalovirus/efectos de los fármacos , Citomegalovirus/fisiología , Herpesvirus Humano 4/efectos de los fármacos , Herpesvirus Humano 4/fisiología , Humanos , Inmunosupresores/farmacología , Cinética , Estudios Retrospectivos
7.
BMC Infect Dis ; 20(1): 509, 2020 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-32664850

RESUMEN

BACKGROUND: Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. This study aimed to identify the relationships among antiviral cytokines produced by natural killer (NK) and T cells and clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients. METHODS: We measured antiviral cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) produced by T, NK and natural killer T (NKT) cells, respectively, in a cohort with chronic hepatitis B virus (HBV) infection (CHB). We also correlated these cytokines with clinical-virological characteristics using a linear regression model. RESULTS: levels of IFN-γ+ and TNF-α+ CD4+ and CD8+ T cells were significantly higher in immune active (IA) phase than in other phases. Immune tolerant (IT) patients showed the lowest expression of IFN-γ by NK and NKT cells, and TNF-α by NK cells. IFN-γ+, TNF-α+ and IL-2+ CD4+ and CD8+ T cells frequencies were similar between IA and gray zone (GZ) phases. Principal component analysis based on cytokines confirmed that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. Multivariate analysis showed both T and NK cells producing IFN-γ and TNF-α, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-γ+ NKT cells were associated with HBV DNA, while IFN-γ+ CD4+ and CD8+ T cells were correlated with age. CONCLUSION: HBV clinical phases are characterized by distinct cytokine signatures, which showed relationship to viral features in these untreated CHB patients.


Asunto(s)
Inmunidad Adaptativa , Citocinas/metabolismo , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/inmunología , Inmunidad Innata , Adulto , Alanina Transaminasa/sangre , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Estudios de Cohortes , ADN Viral/sangre , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/virología , Humanos , Células Asesinas Naturales/inmunología , Masculino , Células T Asesinas Naturales/inmunología , Adulto Joven
8.
Anticancer Res ; 40(7): 3983-3990, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32620641

RESUMEN

BACKGROUND/AIM: Few studies have studied micro hepatic vein invasion in hepatocellular carcinoma (HCC). We explored the correlation between hepatic vein invasion and hepatitis B/C virus infection. PATIENTS AND METHODS: Between April 2000 and February 2018, 869 patients underwent liver resection for HCC at a single center. The patients were divided into two groups: those with micro hepatic vein invasion (VV+) and those without (VV-). The clinical data, overall survival (OS) and correlations with the presence of hepatitis B and C viruses were investigated. RESULTS: There were 817 VV- patients and 43 VV+ patients. OS was 66.2 months for VV- patients and 9.9 months for VV+ patients (p=0.0010). VV+ patients had significantly higher levels of serum HBV DNA (p=0.016). CONCLUSION: HCC patients with micro hepatic vein invasion showed significantly shorter OS. A higher level of HBV DNA appears to be a risk factor for micro hepatic vein invasion.


Asunto(s)
Carcinoma Hepatocelular/patología , Venas Hepáticas/patología , Neoplasias Hepáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Virales/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , ADN Viral/sangre , Femenino , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis B/patología , Hepatitis B/virología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis C/patología , Hepatitis C/virología , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Adulto Joven
9.
Proc Natl Acad Sci U S A ; 117(31): 18692-18700, 2020 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-32690683

RESUMEN

A scalable approach for quantifying intact HIV-1 proviruses is critical for basic research and clinical trials directed at HIV-1 cure. The intact proviral DNA assay (IPDA) is a novel approach to characterizing the HIV-1 reservoir, focusing on the genetic integrity of individual proviruses independent of transcriptional status. It uses multiplex digital droplet PCR to distinguish and separately quantify intact proviruses, defined by a lack of overt fatal defects such as large deletions and APOBEC3G-mediated hypermutation, from the majority of proviruses that have such defects. This distinction is important because only intact proviruses cause viral rebound on ART interruption. To evaluate IPDA performance and provide benchmark data to support its implementation, we analyzed peripheral blood samples from 400 HIV-1+ adults on ART from several diverse cohorts, representing a robust sample of treated HIV-1 infection in the United States. We provide direct quantitative evidence that defective proviruses greatly outnumber intact proviruses (by >12.5 fold). However, intact proviruses are present at substantially higher frequencies (median, 54/106 CD4+ T cells) than proviruses detected by the quantitative viral outgrowth assay, which requires induction and in vitro growth (∼1/106 CD4+ T cells). IPDA amplicon signal issues resulting from sequence polymorphisms were observed in only 6.3% of individuals and were readily apparent and easily distinguished from low proviral frequency, an advantage of the IPDA over standard PCR assays which generate false-negative results in such situations. The large IPDA dataset provided here gives the clearest quantitative picture to date of HIV-1 proviral persistence on ART.


Asunto(s)
ADN Viral/sangre , Infecciones por VIH , Provirus/genética , Latencia del Virus/genética , Adulto , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos
10.
PLoS One ; 15(6): e0234773, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32559248

RESUMEN

Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death worldwide. Patients with hepatitis B virus (HBV) pre-S mutants in liver tissues or blood have been regarded as a high-risk population for HCC development and recurrence. Detection of pre-S mutants in clinical specimens is thus important for early diagnosis and prognosis of HCC to improve patient survival. Recently, we have developed a next-generation sequencing (NGS)-based platform that can quantitatively detect pre-S mutants in patient plasma with superior sensitivity and accuracy. In this study, we compared the pre-S genotyping results from plasma by the NGS-based analysis with those from liver tissues by the immunohistochemistry (IHC)-based analysis in 30 HBV-related HCC patients. We demonstrated that the detection rate of pre-S mutants was significantly higher by NGS- than by IHC-based analysis. There was a moderate to good agreement between both analyses in detection of pre-S mutants. Compared with the IHC, the NGS-based detection of pre-S mutants in patient plasma could determine the patterns of pre-S mutants in liver tissues more efficiently in a noninvasive manner. Our data suggest that the NGS-based platform may represent a promising approach for detection of pre-S mutants as biomarkers of HBV-related HCC in clinical practice.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Hígado/virología , Precursores de Proteínas/genética , Adulto , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , ADN Viral/sangre , ADN Viral/metabolismo , Femenino , Genotipo , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Hígado/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Mutación , Precursores de Proteínas/sangre , Análisis de Secuencia de ADN
11.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(6): 902-907, 2020 Jun 10.
Artículo en Chino | MEDLINE | ID: mdl-32564557

RESUMEN

Objective: To analyze the relationship between maternal mutations in basal core promoter region of hepatitis B virus (HBV) genotype C and intrauterine transmission. Methods: We collected information on general demographic characteristics and process of delivery among 399 pairs of consecutive HBsAg-positive mothers and their neonates, from the Third People's Hospital of Taiyuan in Shanxi province, China. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and Electro-chemiluminescence immuno-assay (ECLIA) kits were used to detect both maternal and neonatal HBV DNA and serological markers in the peripheral blood. From 113 mothers with HBV DNA load ≥10(6) IU/ml, we selected 22 mothers whose neonates were with intrauterine transmission and randomly selected the same number of mothers whose neonates were without intrauterine transmission, as controls. The whole-length HBV DNA were extracted, amplified, cloned, sequenced and genotyped. Finally, a total of 39 mothers with genotype C of HBV were selected for mutation analysis. Results: Thirty-nine cases of genotype C (88.63%) were finally included in the study, with 19 cases in the intrauterine transmission group and 20 cases as controls. Rates of A1762T/G1764A double mutations were significantly different between the intrauterine transmission group and the control group (7.53% vs. 27.72%, P<0.001). Results from the multivariate analysis showed that the A1762T/G1764A double mutations had reduced the risk of intrauterine transmission (aOR=0.065, 95%CI: 0.006-0.746, P=0.028). Maternal A1762T/G1764A double mutations appeared to be possibly associated with neonatal HBeAg (P=0.050). Conclusion: A1762T/G1764A double mutations of HBV DNA from the genotype C of those HBsAg-positive mothers could reduced the risk of HBV intrauterine transmission during pregnancy.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Mutación , Complicaciones Infecciosas del Embarazo/virología , Regiones Promotoras Genéticas/genética , China , ADN Viral/sangre , Femenino , Genotipo , Humanos , Recién Nacido , Embarazo
12.
Int J Infect Dis ; 97: 126-130, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32497807

RESUMEN

OBJECTIVE: The aim of this study was to determine the OBI in plasma and urine samples from renal transplant patients using Multiplex Nested PCR. METHOD: A total of 100 samples (plasma and urine) were collected from renal transplant patients admitted to the renal transplant center in Khartoum north, Sudan in 2019. For each sample, HBsAg, HBeAg and anti HBcAg were detected using Enzyme linked Immune sorbent assay (ELISA). The viral DNA was then extracted using viral DNA extraction kit and were then tested for HBV DNA by using multiplex nested PCR. Statistical analysis was done using statistical package of social science (IBM SPSS version 20.0) considering a P value ≤ 0.05 as a level of significance. RESULTS: HBsAg were not detected in al patient but, HBeAg were 14 (14%) and anti HBcAg were 36 (36%)were detect by using ELISA. A total 18 (18%) and 3 out of 100 were found positive in plasma and urine samples, respectively. Regarding the virus genotypes, D, E and mixed D/E genotypes were detected in all positive samples. Females were significantly (P value=0.013) higher detectable with HBV than males in plasma samples CONCLUSION: OBI incidence in renal transplant patients is high in Sudan. The multiplex nested PCR had identified OBI with a high rate supporting the efficiency of using molecular techniques in detecting of HBV. This will lead to an appropriate diagnosis and minimizing the risk to be infected by HBV.


Asunto(s)
Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/virología , Trasplante de Riñón , Adulto , Estudios Transversales , ADN Viral/sangre , Femenino , Genotipo , Hepatitis B/sangre , Hepatitis B/orina , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Sudán
13.
J Med Microbiol ; 69(6): 812-816, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32469303

RESUMEN

HIV prevalence in Oman is low (<5 %); however, 45 % of the population are expatriates, including a portion originating from countries with high HIV prevalence (>5 %). HIV screening is performed at regional public health laboratories as part of a medical fitness programme for residency applicants. We conducted a retrospective evaluation of indeterminate serology results from 11 females of African origin, aged 21-43 years. Serology testing for HIV was conducted according to the national Oman algorithm: fourth-generation immunoassays (Bio-Rad GS HIV Combo Ag/Ab EIA, Siemens Enzygnost HIV Integral 4, Abbott ARCHITECT HIV Ag/Ab Combo, Roche Elecsys HIV Combi PT, bioMérieux VIDAS HIV DUO QUICK), confirmatory assays (Geenius HIV 1/2 Confirmatory, INNO-LIA HIV I/II Score) and PCR testing. Confirmatory testing to resolve indeterminate results was conducted with available samples for five patients using a combination of immunoassays, confirmatory assays, PCR/PERT and pro-viral DNA levels, at three external laboratories; Roche Diagnostics (Germany), Swiss National Laboratory (Switzerland) and Barts Health NHS Trust (UK). Nineteen serum, 15 plasma and two whole-blood samples were analysed. Nine of ten patients analysed on Bio-Rad and Siemens immunoassays were highly reactive; seven were highly reactive on the Abbott assay. Eight of nine patients tested with the Roche assay were negative. Three of four patients tested on the bioMérieux assay were negative. Five patients underwent confirmatory testing at external laboratories; all were negative by HIV-RNA or pro-viral DNA testing. In conclusion, HIV-RNA and pro-viral DNA testing is recommended for HIV screening of individuals from high-prevalence regions coming to low-prevalence regions.


Asunto(s)
ADN Viral/sangre , Infecciones por VIH/diagnóstico , ARN Viral/sangre , Adulto , Reacciones Falso Positivas , Femenino , Infecciones por VIH/sangre , Humanos , Estudios Retrospectivos , Adulto Joven
14.
Sci Rep ; 10(1): 7894, 2020 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-32398741

RESUMEN

Understanding patterns of pathogen emergence can help identify mechanisms involved in transmission dynamics. Beak and feather disease virus (BFDV) poses a major threat world-wide to wild and captive parrots. Yet data from wild birds on seasonal fluctuations in prevalence and infection intensity, and thereby the potential high-risk times for virus transmission, have been lacking. We screened wild Crimson Rosellas (Platycercus elegans) for BFDV in blood and cloacal swabs. Prevalence in blood samples and cloacal swabs, as well as viral load varied with Julian date and in blood, were highest after the breeding season. Breeding birds had lower viral load and lower BFDV prevalence in blood than non-breeding birds (10.1% prevalence in breeding vs. 43.2% in non-breeding birds). BFDV prevalence was much higher in younger (<3 years) than older (≥3 years) birds for both blood samples (42.9% vs. 4.5%) and cloacal swabs (56.4% vs. 12.3%). BFDV status in blood and cloacal samples was not correlated within individuals. We show that, at least in P. elegans, BFDV infection seems to occur year-round, with seasonal changes in prevalence and load found in our samples. Our analyses suggest that the seasonal changes were associated primarily with the breeding season. We also discuss age and sex as important predictors of BFDV infection.


Asunto(s)
Animales Salvajes/fisiología , Enfermedades de las Aves/transmisión , Infecciones por Circoviridae/veterinaria , Loros/fisiología , Estaciones del Año , Animales , Animales Salvajes/virología , Australia/epidemiología , Enfermedades de las Aves/virología , Cruzamiento , Infecciones por Circoviridae/epidemiología , Infecciones por Circoviridae/virología , Circovirus/genética , Circovirus/fisiología , ADN Viral/sangre , ADN Viral/genética , Femenino , Masculino , Loros/virología , Prevalencia , Análisis de Secuencia de ADN , Carga Viral/genética
15.
Aliment Pharmacol Ther ; 51(12): 1406-1416, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32390175

RESUMEN

BACKGROUND: Virus, host factors and their interplay influence Hepatitis B surface Antigen serum levels during Hepatitis B Virus (HBV) infection course and treatment. AIM: To study the Pre-S/S circulating quasispecies in a cohort of untreated, HBeAg negative, genotype-D, HBsAg carriers. METHODS: We studied 260 carriers: 71 with HBeAg negative infection (ENI; HBV-DNA ≤2000 IU/mL); 42 Grey Zone (GZ; HBV-DNA ≤20 000 IU/mL); 82 chronic hepatitis (CH) and 65 cirrhosis (CI) (HBV-DNA > 20 000 IU/mL). Population sequencing was applied to identify Pre-S/S gene mutations responsible for any amino acid substitution or potential biological/antigenic implications (M-muts) on HBsAg. RESULTS: HBsAg serum levels were lower in ENI + GZ than in CH + CI (2.61 [-1.10/4.06] vs 3.62 [2.41/4.92] log10 IU/mL, P < 0.001) and in CI than CH (3.48 [2.41/4.38] vs 3.66 [2.57/4.92] log10 IU/mL, P < 0.001). M-muts were found in 73 (28.1%) cases: 5 (7.0%) ENI, 3 (7.1%) GZ, 26 (31.7%) CH, 39 (60.0%) CI (P < 0.001) and mostly in Pre-S2 (17.6%) than Pre-S1 (5.8%) and Small-S (10.8%; P < 0.001). Overall HBsAg serum levels were higher in carriers with M-muts (3.56 [0.95/4.38] vs 3.17 [-1.10/4.92] log10 IU/mL, P < 0.001), but comparable in carriers with or without M-mut when considering separately ENI + GZ (2.84 [0.95/3.89] vs 2.61 [-1.10/4.06] log10 IU/mL, P = 0.330] and CH + CI (3.57 [2.67/4.38] vs 3.63 [2.41/4.92] log10 IU/mL, P = 0.37). Infection phase (ß: 0.422, P < 0.001), age (ß: -0.260, P < 0.001), ALT (ß: -0.103, P = 0.045), liver stiffness (ß: -0.118, P = 0.039) and HBV-DNA (ß: 0.384, P < 0.001), but not M-mut were independently associated with HBsAg serum levels. CONCLUSIONS: In HBeAg negative, genotype-D, carriers Pre-S/S heterogeneity increases with severity of liver disease, but does not influence HBsAg serum levels, that in low viraemic carriers are associated with an effective control of HBV.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Hepatitis B/sangre , Cuasiespecies , Adolescente , Adulto , Anciano , Portador Sano/sangre , Portador Sano/virología , Estudios de Cohortes , ADN Viral/sangre , Progresión de la Enfermedad , Femenino , Genotipo , Hepatitis B/patología , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/análisis , Antígenos e de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pruebas Serológicas , Viremia/sangre , Viremia/virología , Adulto Joven
16.
Lancet HIV ; 7(5): e359-e365, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32386722

RESUMEN

Several assays have been developed to measure and characterise the replication-competent HIV-1 reservoir, which constitutes the barrier to cure. To date, the application of these assays to studies in children and in limited-resource settings has been minimal, primarily because of their expense, the large required blood volumes, and labour-intensive technologies. For children vertically infected with HIV-1 who initiated suppressive antiretroviral therapy (ART) regimens in infancy, HIV-1-specific antibody concentrations are associated with viral persistence and could be used to estimate the size of the residual latent reservoir on ART. This strategy could be particularly useful for screening children on suppressive ART for enrolment into therapeutic vaccine trials and other protocols aimed at achieving HIV-1 remission.


Asunto(s)
Anticuerpos Anti-VIH/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Transmisión Vertical de Enfermedad Infecciosa , Carga Viral , Fármacos Anti-VIH/uso terapéutico , ADN Viral/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Humanos , Lactante
17.
J Virol ; 94(14)2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32350073

RESUMEN

Antiretroviral therapy (ART) cannot eradicate human immunodeficiency virus (HIV) and a rapid rebound of virus replication follows analytical treatment interruption (ATI) in the vast majority of HIV-infected individuals. Sustained control of HIV replication without ART has been documented in a subset of individuals, defined as posttreatment controllers (PTCs). The key determinants of post-ART viral control remain largely unclear. Here, we identified 7 SIVmac239-infected rhesus macaques (RMs), defined as PTCs, who started ART 8 weeks postinfection, continued ART for >7 months, and controlled plasma viremia at <104 copies/ml for up to 8 months after ATI and <200 copies/ml at the latest time point. We characterized immunologic and virologic features associated with post-ART SIV control in blood, lymph node (LN), and colorectal (RB) biopsy samples compared to 15 noncontroller (NC) RMs. Before ART initiation, PTCs had higher CD4 T cell counts, lower plasma viremia, and SIV-DNA content in blood and LN compared to NCs, but had similar CD8 T cell function. While levels of intestinal CD4 T cells were similar, PTCs had higher frequencies of Th17 cells. On ART, PTCs had significantly lower levels of residual plasma viremia and SIV-DNA content in blood and tissues. After ATI, SIV-DNA content rapidly increased in NCs, while it remained stable or even decreased in PTCs. Finally, PTCs showed immunologic benefits of viral control after ATI, including higher CD4 T cell levels and reduced immune activation. Overall, lower plasma viremia, reduced cell-associated SIV-DNA, and preserved Th17 homeostasis, including at pre-ART, are the main features associated with sustained viral control after ATI in SIV-infected RMs.IMPORTANCE While effective, antiretroviral therapy is not a cure for HIV infection. Therefore, there is great interest in achieving viral remission in the absence of antiretroviral therapy. Posttreatment controllers represent a small subset of individuals who are able to control HIV after cessation of antiretroviral therapy, but characteristics associated with these individuals have been largely limited to peripheral blood analysis. Here, we identified 7 SIV-infected rhesus macaques that mirrored the human posttreatment controller phenotype and performed immunologic and virologic analysis of blood, lymph node, and colorectal biopsy samples to further understand the characteristics that distinguish them from noncontrollers. Lower viral burden and preservation of immune homeostasis, including intestinal Th17 cells, both before and after ART, were shown to be two major factors associated with the ability to achieve posttreatment control. Overall, these results move the field further toward understanding of important characteristics of viral control in the absence of antiretroviral therapy.


Asunto(s)
Antirretrovirales/farmacología , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Células Th17 , Animales , Relación CD4-CD8 , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , ADN Viral/sangre , ADN Viral/inmunología , Macaca mulatta , Síndrome de Inmunodeficiencia Adquirida del Simio/sangre , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/inmunología , Virus de la Inmunodeficiencia de los Simios/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Factores de Tiempo
18.
J Oral Pathol Med ; 49(7): 693-700, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32428250

RESUMEN

INTRODUCTION: The role of viral infections in the pathogenesis of autoimmune diseases has long been suggested, but little evidence is available. OBJECTIVE: This study aimed to evaluate an association between EBV and CMV and the presence of rheumatoid arthritis and its association with Sjögren's Syndrome. PATIENTS AND METHOD: A case-control study was performed with 227 patients divided in RA (n = 99), RA/SS (n = 20), and C (n = 128). Resting salivary flow rate and Schirmer's test were performed; minor salivary gland biopsy was indicated in the case of suspected Sjögren's syndrome. CMV and EBV viral loads were quantified in peripheral blood, and their presence in glandular tissue samples was evaluated by in situ hybridization (EBV) and immunohistochemistry (CMV). RESULTS: EBV was more frequent in RA and RA/SS than in C (P < .000007). No correlation with clinical markers (P > .05) or between RA and RA/SS was found (P > .05). A higher number of EBV/DNA copies were found in RA (158.52 copies/µL) and RA/SS (99.24 copies/µL) (P = .739). EBV/DNA was associated with the Schirmer test (P = .0231). CMV was detected in one patient of the RA group. None of the viruses were detected in biopsies of minor salivary glands. CONCLUSIONS: Detection of EBV/DNA in peripheral blood was associated with RA regardless of the presence of SS.


Asunto(s)
Artritis Reumatoide/virología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Virus de Epstein-Barr/complicaciones , Síndrome de Sjögren/virología , Carga Viral , Artritis Reumatoide/complicaciones , Estudios de Casos y Controles , ADN Viral/sangre , Herpesvirus Humano 4 , Humanos , Síndrome de Sjögren/complicaciones
19.
Aliment Pharmacol Ther ; 52(1): 196-204, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32452564

RESUMEN

BACKGROUND: Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase. AIMS: To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase. METHODS: In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes. RESULTS: The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log10 IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >107  IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001). CONCLUSIONS: The criterion of HBV-DNA level > 107  IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.


Asunto(s)
Carcinoma Hepatocelular/epidemiología , Hepatitis B Crónica/epidemiología , Neoplasias Hepáticas/epidemiología , Adulto , Alanina Transaminasa/sangre , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/virología , ADN Viral/sangre , Femenino , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Tolerancia Inmunológica , Incidencia , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
20.
Int J Hematol ; 112(2): 193-199, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32472530

RESUMEN

Posttransplant lymphoproliferative disorder (PTLD) after allogeneic hematopoietic cell transplantation (HCT) is usually donor derived, associated with Epstein-Barr virus (EBV), and of B-cell origin. T-cell PTLD (T-PTLD) after allogeneic HCT is extremely rare. Four of 1015 (0.39%) allogeneic HCT patients were diagnosed with T-PTLD; peripheral T-cell lymphoma-not otherwise specified, anaplastic large cell lymphoma, monomorphic T-cell PTLD and polymorphic PTLD with chronic active EBV infection-like symptoms. Three of the four patients developed T-PTLD within 6 months after HCT from HLA-mismatched unrelated donor. Three (75%) and 4 (100%) cases were positive for EBV-encoded small RNA in situ hybridization and EBV-DNA load in peripheral blood, respectively. Chimerism analysis showed that 75% of T-PTLD tissues (3/4) were recipient derived. T-PTLD was refractory to salvage chemotherapy and fatal in all four patients. Including the 10 patients in the literature, the median interval from HCT to diagnosis of T-PTLD was 5 months (range 1-72 months), 55% were negative for EBV, and 56% were recipient-derived. T-PTLD, which often occurred early after allogeneic HCT, was more likely to be EBV negative and recipient derived than B-cell PTLD after allogeneic HCT. Like T-PTLD after solid organ transplant, T-PTLD after allogeneic HCT demonstrated morphological heterogeneity and poor prognosis.


Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Linfoproliferativos/etiología , Linfocitos T , Niño , Preescolar , ADN Viral/sangre , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Femenino , Herpesvirus Humano 4 , Humanos , Hibridación in Situ , Lactante , Masculino , Pronóstico , Trasplante Homólogo , Carga Viral
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