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3.
Microorganisms ; 11(12)2023 Nov 21.
Article in English | MEDLINE | ID: mdl-38137968

ABSTRACT

Although uncommon, Epstein-Barr virus-related neurological disorders represent the seventh most frequent cause of infectious encephalitis in adults. The limited number of publications on EBV encephalitis mainly document isolated clinical cases. This study aimed to summarize published data on EBV encephalitis. A systematic literature search identified 97 EBV encephalitis cases. In the selected cases, EBV-related neurological disorders manifested as lymphocytic pleocytosis in the cerebrospinal fluid (CSF) with moderate hyperproteinorachia. The EBV PCR test was positive in 87% of the CSF samples, with wide-ranging viral loads. When encephalitis occurred in the context of past EBV infections, all of the EBV PCR tests on CSF samples were positive. On the contrary, negative EBV PCR tests on CSF samples occurred only in the context of primary infections. EBV PCR was rarely carried out on blood samples, contributing minimally to the diagnosis. For the treatment of EBV encephalitis, Aciclovir was used alone in 29% of cases, and in association with other drugs in 40% of cases. Ganciclovir (30%), corticoids (52%), and immunoglobulins (15%) were mainly used in association with other drugs. Cerebral imaging was abnormal in 69% of cases, mostly in the cerebellum and basal ganglia. This work highlights that the EBV PCR test on CSF samples is currently the main laboratory diagnostic test to diagnose EBV encephalitis. This diagnostic test is useful; however, it is imperfect. New complementary diagnostic tools, approved treatments, and standardized practices could improve patient management.

5.
Int J Antimicrob Agents ; 61(5): 106769, 2023 May.
Article in English | MEDLINE | ID: mdl-36870404

ABSTRACT

Herpes simplex virus 2 (HSV-2) rarely causes severe disease, even in solid organ transplant recipients. This paper describes a fatal case of HSV-2 infection, probably transmitted from a donor to a kidney transplant recipient. The donor was seropositive for HSV-2 but not for HSV-1, whereas the recipient was seronegative for both viruses before transplantation, suggesting that the graft was the source of infection. The recipient received valganciclovir prophylaxis due to cytomegalovirus seropositivity. Three months after transplantation, the recipient presented with rapidly disseminated cutaneous HSV-2 infection with meningoencephalitis. The HSV-2 strain was resistant to acyclovir, probably acquired under valganciclovir prophylaxis. Despite early initiation of acyclovir therapy, the patient died. This fatal case of HSV-2 infection, probably transmitted by the kidney graft with acyclovir-resistant HSV-2 from the onset, is uncommon.


Subject(s)
Herpes Simplex , Herpesvirus 2, Human , Kidney Transplantation , Herpes Simplex/diagnosis , Herpes Simplex/drug therapy , Fatal Outcome , Antiviral Agents/therapeutic use , Humans
6.
Viruses ; 15(3)2023 02 28.
Article in English | MEDLINE | ID: mdl-36992365

ABSTRACT

Epstein-Barr virus (EBV) is an oncogenic virus infecting more than 95% of the world's population. After primary infection-responsible for infectious mononucleosis in young adults-the virus persists lifelong in the infected host, especially in memory B cells. Viral persistence is usually without clinical consequences, although it can lead to EBV-associated cancers such as lymphoma or carcinoma. Recent reports also suggest a link between EBV infection and multiple sclerosis. In the absence of vaccines, research efforts have focused on virological markers applicable in clinical practice for the management of patients with EBV-associated diseases. Nasopharyngeal carcinoma is an EBV-associated malignancy for which serological and molecular markers are widely used in clinical practice. Measuring blood EBV DNA load is additionally, useful for preventing lymphoproliferative disorders in transplant patients, with this marker also being explored in various other EBV-associated lymphomas. New technologies based on next-generation sequencing offer the opportunity to explore other biomarkers such as the EBV DNA methylome, strain diversity, or viral miRNA. Here, we review the clinical utility of different virological markers in EBV-associated diseases. Indeed, evaluating existing or new markers in EBV-associated malignancies or immune-mediated inflammatory diseases triggered by EBV infection continues to be a challenge.


Subject(s)
Epstein-Barr Virus Infections , Lymphoma , Lymphoproliferative Disorders , Nasopharyngeal Neoplasms , Humans , Herpesvirus 4, Human/genetics , Lymphoproliferative Disorders/complications
7.
J Med Virol ; 95(1): e28166, 2023 01.
Article in English | MEDLINE | ID: mdl-36137986

ABSTRACT

Serological markers for Epstein-Barr virus (EBV) infection are commonly used to diagnose infectious mononucleosis and establish a serological status in pretransplant patients. This study prospectively assessed 1043 serum specimens sent to the laboratory for physician-ordered EBV testing. The three markers-antiviral capsid antigen (VCA) immunoglobulin M (IgM), anti-VCA immunoglobulin G (IgG), and anti-Epstein-Barr nuclear antigen (EBNA) antibodies-were tested using the Elecsys and the Liaison immunoassays. Specimens with discrepant results between the two assays were assessed using further EBV diagnostic approaches to conclude on the EBV serological status. In spite of substantial agreement between the two assays (88%) and with the presumed EBV status (>92%), the results showed differences in the performance of the assays. Liaison VCA IgM appeared to be the most sensitive test for the detection of the 38 sera classified as early primary infection in comparison with the Elecsys assay (91.4% vs. 68.6%, p = 0.008). Excluding the cases of early primary infection, the sensitivity values of the VCA IgM marker were comparable between the Liaison and Elecsys assays (95.2% and 92.9%, respectively, p = 1). Concerning the sera classified as past infection (n = 763), the Elecsys assay showed higher sensitivity values for the detection of the VCA and EBNA IgG markers in comparison with the Liaison assay (99.9% and 99.7% vs. 97.4% and 91.2%, respectively, p < 0.001). Overall, the Elecsys and Liaison assays showed similar performance. The interpretation of EBV serological profiles based on the clinical context may require serology follow up or further diagnostic approaches in challenging cases.


Subject(s)
Epstein-Barr Virus Infections , Humans , Herpesvirus 4, Human , Sensitivity and Specificity , Immunoassay/methods , Immunoglobulin M , Immunoglobulin G , Antibodies, Viral , Antigens, Viral
8.
Vaccine ; 40(44): 6404-6411, 2022 10 19.
Article in English | MEDLINE | ID: mdl-36184404

ABSTRACT

BACKGROUND: A fourth dose of SARS-CoV-2 vaccine is recommended in solid-organ transplant (SOT) recipients, but the immunogenicity is poorly known. METHODS: We conducted a retrospective, observational, monocentric study between the 1st January 2021 and 31st March 2022 of the anti-Spike antibody titers after one to four doses of vaccine in SOT. RESULTS: 825 SOT were included. Median age at first vaccine injection was 61.2 (IQR 50.9-69.3) years; 66.7 % were male; 63.4 % had received four vaccine doses. The proportion of participants with a strong humoral response (>260 BAU/mL) increased with the number of vaccine doses: 10.6 % after the 1st dose (D1), 35.1 % after the 2nd (D2), 48.5 % after the 3rd (D3), and 65.1 % after the 4th (D4) (p < 0.001). Among the tested patients, the proportion with a detectable humoral response was significantly higher after D4 than after D3 (47 % vs 22 %, p = 0.01). Liver transplant recipients had more frequently a strong humoral response after D2, D3 and D4 (OR = 5.3, 3.7 and 6.6 respectively when compared with other organ transplant recipients, p < 0.001). In kidney transplant recipients, belatacept-containing regimen was associated with a lower rate of detectable humoral (9 % vs 40 %, p = 0.025) after D3, but there was no statistical difference after D4. CONCLUSION: A fourth dose should be proposed to SOT recipients who did not developed an immune response after 3 doses. Kidney transplant recipients receiving belatacept have a poorer, although frequently detectable response.


Subject(s)
COVID-19 , Organ Transplantation , Adult , Humans , Male , Middle Aged , Aged , Female , COVID-19 Vaccines , SARS-CoV-2 , Retrospective Studies , Abatacept , COVID-19/prevention & control , Antibodies, Viral , Transplant Recipients
9.
Infect Dis Now ; 52(8): 453-455, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36108970

ABSTRACT

Real-time PCR plays a key role in the diagnosis of viral infections. Multiple kits can detect or quantify genomes of various viruses with the same thermocycling program. Detection of RNA viruses includes an additional step of reverse transcription and challenge their detection in a single run with DNA viruses. We investigated the analytical performance of HSV-1, HSV-2 and VZV DNA quantification with Altona RealStar® PCR kits using the RT-PCR program for RNA viruses instead of the PCR program for DNA viruses. For each three viruses, Bland-Altman distribution did not show differences between both programs, and quantification curves generated with both thermocycling programs confirmed high correlation (R2 ≥ 0.9983). Detection of low viral load samples was evaluated, on 10-times repeat-test. All replicate samples were detected with both thermocycling programs and were quantified at similar viral loads (bias in log10 copies/mL: +0.05 (HSV-1), -0.01 (HSV-2) and +0.25 (VZV)). This confirms the feasibility of using the RT-PCR thermocycling program to detect and quantify the genome of RNA and DNA viruses in a single run.


Subject(s)
RNA Viruses , Humans , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Real-Time Polymerase Chain Reaction , DNA Viruses
10.
Pathogens ; 11(8)2022 Aug 17.
Article in English | MEDLINE | ID: mdl-36015048

ABSTRACT

The ZEBRA (Z EBV replication activator) protein is the major transcription factor of EBV, expressed upon EBV lytic cycle activation. An increasing body of studies have highlighted the critical role of EBV lytic infection as a risk factor for lymphoproliferative disorders, such as post-transplant lymphoproliferative disease (PTLD). We studied 108 transplanted patients (17 PTLD and 91 controls), retrospectively selected from different hospitals in France and in the Netherlands. The majority of PTLD were EBV-positive diffuse large B-cell lymphomas, five patients experienced atypical PTLD forms (EBV-negative lymphomas, Hodgkin's lymphomas, and T-cell lymphomas). Fourteen patients among the seventeen who developed a pathologically confirmed PTLD were sZEBRA positive (soluble ZEBRA, plasma level above 20 ng/mL, measured by an ELISA test). The specificity and positive predictive value (PPV) of the sZEBRA detection in plasma were 98% and 85%, respectively. Considering a positivity threshold of 20 ng/mL, the sensitivity of the sZEBRA was 82.35% and the specificity was 94.51%. The mean of the sZEBRA values in the PTLD cases were significantly higher than in the controls (p < 0.0001). The relevance of the lytic cycle and, particularly, the role of ZEBRA in lymphomagenesis is a new paradigm pertaining to the prevention and treatment strategies for PTLD. Given the high-specificity and the predictive values of this test, it now appears relevant to investigate the lytic EBV infection in transplanted patients as a prognostic biomarker.

12.
Nucleic Acids Res ; 50(1): 490-511, 2022 01 11.
Article in English | MEDLINE | ID: mdl-34893887

ABSTRACT

In infected cells, Epstein-Barr virus (EBV) alternates between latency and lytic replication. The viral bZIP transcription factor ZEBRA (Zta, BZLF1) regulates this cycle by binding to two classes of ZEBRA response elements (ZREs): CpG-free motifs resembling the consensus AP-1 site recognized by cellular bZIP proteins and CpG-containing motifs that are selectively bound by ZEBRA upon cytosine methylation. We report structural and mutational analysis of ZEBRA bound to a CpG-methylated ZRE (meZRE) from a viral lytic promoter. ZEBRA recognizes the CpG methylation marks through a ZEBRA-specific serine and a methylcytosine-arginine-guanine triad resembling that found in canonical methyl-CpG binding proteins. ZEBRA preferentially binds the meZRE over the AP-1 site but mutating the ZEBRA-specific serine to alanine inverts this selectivity and abrogates viral replication. Our findings elucidate a DNA methylation-dependent switch in ZEBRA's transactivation function that enables ZEBRA to bind AP-1 sites and promote viral latency early during infection and subsequently, under appropriate conditions, to trigger EBV lytic replication by binding meZREs.


Subject(s)
DNA, Viral/metabolism , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/genetics , Trans-Activators/metabolism , Viral Proteins/metabolism , DNA Methylation , Gene Expression Regulation, Viral , HEK293 Cells , Humans , Protein Binding , Virus Replication
15.
J Clin Virol ; 143: 104947, 2021 10.
Article in English | MEDLINE | ID: mdl-34492569

ABSTRACT

Robust antigen point-of-care SARS-CoV-2 tests have been proposed as an efficient tool to address the COVID-19 pandemic. This requirement was raised after acknowledging the constraints that are brought by molecular biology. However, worldwide markets have been flooded with cheap and potentially underperforming lateral flow assays. Herein we retrospectively compared the overall performance of five qualitative rapid antigen SARS-CoV-2 assays and one quantitative automated test on 239 clinical swabs. While the overall sensitivity and specificity are relatively similar for all tests, concordance with molecular based methods varies, ranging from 75,7% to 83,3% among evaluated tests. Sensitivity is greatly improved when considering patients with higher viral excretion (Ct≤33), proving that antigen tests accurately distinguish infectious patients from viral shedding. These results should be taken into consideration by clinicians involved in patient triage and management, as well as by national authorities in public health strategies and for mass campaign approaches.


Subject(s)
COVID-19 , SARS-CoV-2 , Antigens, Viral , Humans , Nasopharynx , Pandemics , Retrospective Studies , Sensitivity and Specificity
17.
Front Microbiol ; 12: 701611, 2021.
Article in English | MEDLINE | ID: mdl-34239514

ABSTRACT

Epstein-Barr virus (EBV) is one of the most widespread viruses in the world; more than 90% of the planet's adult population is infected. Symptomatic primary infection by this Herpesviridae corresponds to infectious mononucleosis (IM), which is generally a benign disease. While virus persistence is often asymptomatic, it is responsible for 1.5% of cancers worldwide, mainly B cell lymphomas and carcinomas. EBV may also be associated with autoimmune and/or inflammatory diseases. However, no effective treatment or anti-EBV vaccine is currently available. Knowledge of the proteins and mechanisms involved in the different steps of the viral cycle is essential to the development of effective vaccines. The present review describes the main actors in the entry of the virus into B cells and epithelial cells, which are targets of interest in the development of prophylactic vaccines aimed at preventing viral infection. This review also summarizes the first vaccinal approaches tested in humans, all of which are based on the gp350/220 glycoprotein; while they have reduced the risk of IM, they have yet to prevent EBV infection. The main proteins involved in the EBV latency cycle and some of the proteins involved in the lytic cycle have essential roles in the oncogenesis of EBV. For that reason, these proteins are of interest for the development of therapeutic vaccines of which the objective is the stimulation of T cell immunity against EBV-associated cancers. New strategies aimed at broadening the antigenic spectrum, are currently being studied and will contribute to the targeting of the essential steps of the viral cycle, the objective being to prevent or treat the diseases associated with EBV.

18.
Sci Rep ; 11(1): 14977, 2021 07 22.
Article in English | MEDLINE | ID: mdl-34294751

ABSTRACT

A comprehensive clinical and microbiological assessments of COVID-19 in front-line healthcare workers (HCWs) is needed. Between April 10th and May 28th, 2020, 319 HCWs with acute illness were reviewed. In addition to SARS-CoV-2 RT-PCR screening, a multiplex molecular panel was used for testing other respiratory pathogens. For SARS-CoV-2 positive HCWs, the normalized viral load, viral culture, and virus neutralization assays were performed weekly. For SARS-CoV-2 negative HCWs, SARS-CoV-2 serological testing was performed one month after inclusion. Among the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; 65/67 (97.0%) developed mild form of COVID-19. Other respiratory pathogens were found in 6/66 (9.1%) SARS-CoV-2 positive and 47/241 (19.5%) SARS-Cov-2 negative HCWs (p = 0.07). The proportion of HCWs with a viral load > 5.0 log10 cp/mL (Ct value < 25) was less than 15% at 8 days after symptom onset; 12% of HCWs were positive after 40 days (Ct > 37). More than 90% of cultivable virus had a viral load > 4.5 log10 cp/mL (Ct < 26) and were collected within 10 days after symptom onset. Among negative HCWs, 6/190 (3.2%) seroconverted. Our data suggest that the determination of viral load can be used for appreciating the infectiousness of infected HCWs. These data could be helpful for facilitating their return to work.


Subject(s)
COVID-19/diagnosis , Health Personnel , SARS-CoV-2/isolation & purification , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Female , Humans , Male , Middle Aged , Prospective Studies , Viral Load , Young Adult
19.
Clin Exp Allergy ; 51(7): 947-950, 2021 07.
Article in English | MEDLINE | ID: mdl-33772888

ABSTRACT

Acute attacks could occur during the convalescent phase of COVID-19 illness, more commonly in patients with a history of frequent attacks. However it is unclear whether the acute attacks during the convalescent phase are specifically triggered by COVID-19 or not.


Subject(s)
Angioedemas, Hereditary , COVID-19/metabolism , Registries , Adult , Aged , Aged, 80 and over , Angioedemas, Hereditary/blood , Angioedemas, Hereditary/epidemiology , Angioedemas, Hereditary/therapy , COVID-19/blood , COVID-19/epidemiology , COVID-19/therapy , Female , Humans , Male , Middle Aged , SARS-CoV-2
20.
AIDS ; 35(6): 861-868, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33749224

ABSTRACT

OBJECTIVES: The value of Epstein-Barr virus (EBV) biomarkers on the prognosis of HIV-related non-Hodgkin's lymphoma (NHL) has been poorly explored in the combined antiretroviral therapy (cART) era. DESIGN: We evaluated EBV DNA load and EBV antibodies in HIV-NHL patients enrolled in the French ANRS-CO16 Lymphovir Cohort between 2008 and 2015. METHODS: Whole blood and plasma EBV DNA load and serological profiles were analyzed in 76 HIV-infected patients at diagnosis of NHL and 6 months after the initiation of chemotherapy. RESULTS: Prechemotherapy whole blood (WB) and plasma EBV DNA loads were positive for 80 and 45% of HIV-NHL patients, respectively. Pretreatment WB EBV DNA positivity was associated with a positive plasma HIV-1 RNA load (relative risk (RR), 4.42 [1.33; 14.72]) and plasma EBV DNA positivity with EBV in situ detection (RR 10.62 [2.38; 47.49]). Following chemotherapy, the proportions of patients with positive WB or plasma EBV DNA declined from 81 to 23% (P < 0.0001) and from 43 to 8% (P < 0.0001), respectively. Estimated 2-year progression-free survival did not differ according to prechemotherapy WB positivity (82% versus 67%, P = 0.15) or plasma EBV DNA positivity (76% versus 81%, P  = 0.52). CONCLUSIONS: The plasma EBV DNA load correlates with in situ EBV detection. The WB EBV DNA load correlates with HIV load. WB and plasma EBV DNA loads at NHL diagnosis do not constitute prognostic markers for HIV-NHL patients in the modern cART era.


Subject(s)
Epstein-Barr Virus Infections , HIV Infections , Lymphoma, Non-Hodgkin , DNA, Viral , Epstein-Barr Virus Infections/complications , HIV Infections/complications , HIV Infections/drug therapy , Herpesvirus 4, Human/genetics , Humans , Prospective Studies , Viral Load
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