scholarly journals HIV-exposed infants with EBV infection have a reduced persistence of the immune response to the HBV vaccine

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Silvia Baroncelli ◽  
Clementina Maria Galluzzo ◽  
Giuseppe Liotta ◽  
Mauro Andreotti ◽  
Stefano Orlando ◽  
...  
Keyword(s):  
Humoral Response ◽  
Educational Status ◽  
Infant Growth ◽  
African Countries ◽  
Hbv Vaccine ◽  
Hiv Exposed Infants ◽  
Barr Virus ◽  
Ebv Infection ◽  
Hiv Exposed ◽  
The Impact

Abstract Background In sub-Saharan African countries Epstein Barr virus (EBV) infection occurs in early childhood. We aim to investigate the factors associated with EBV acquisition and the impact of EBV infection on the humoral response to HBV vaccination in infants born from HIV-positive, antiretroviral-treated mothers in Malawi. Methods A total of 149 HIV-exposed infants were included in this longitudinal study. EBV anti-VCA IgG were measured using an ELISA assay. The EBV seroconversion was correlated with the maternal viro-immunological conditions, with infant growth and immunological vulnerability, and with the humoral response to the HBV vaccine. Results No infant was EBV-positive at 6 months (n. 52 tested). More than a third of infants (49/115 or 42.6 %) on study beyond 6 months seroconverted at 12 months. At 24 months, out of 66 tested infants, only 13 remained EBV-uninfected, while 53 (80.3 %) acquired EBV infection, rising the total proportion of EBV seroconversion to 88.7 % (102/115 infants). EBV seroconversion was significantly associated with a low maternal educational status but had no impact on infant growth or vulnerability to infections. Reduced HBsAb levels and accelerated waning of antibodies were associated with early EBV seroconversion. Conclusions We found a heterogeneous timing of acquisition of EBV with the majority of infants born from HIV + mothers acquiring infection after 6 months. Anti-HBs levels were lower and appeared to wane faster in infants acquiring EBV infection.

scholarly journals Toll-Like Receptor (TLR) 9 polymorphism is associated with increased Epstein-Barr virus and Cytomegalovirus acquisition in HIV-exposed infants

AIDS ◽  
2017 ◽  
pp. 1 ◽  
Author(s):  
Kristin Beima-Sofie ◽  
Dalton Wamalwa ◽  
Elizabeth Maleche-Obimbo ◽  
Jairam R. Lingappa ◽  
Romel Mackelprang ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Toll Like Receptor ◽  
Hiv Exposed Infants ◽  
Barr Virus ◽  
Epstein Barr ◽  
Hiv Exposed

scholarly journals Impact of the Umoyo mother-infant pair model on HIV-positive mothers’ social support, perceived stigma and 12-month retention of their HIV-exposed infants in PMTCT Care: Evidence from a cluster randomised control trial in Zambia

2019 ◽  
Author(s):  
Sydney Chauwa Phiri ◽  
Sandra Mudhune ◽  
Margaret L Prust ◽  
Prudence Haimbe ◽  
Hilda Shakwelele ◽  
...  
Keyword(s):  
Public Health ◽  
Social Support ◽  
Health System ◽  
T Test ◽  
Perceived Stigma ◽  
Hiv Exposed Infants ◽  
Pair Model ◽  
Hiv Exposed ◽  
The Impact ◽  
Infant Pair

Abstract Background Public health systems in resource-constrained settings have a critical role to play in the elimination of HIV transmission but are often financially constrained. This study is an evaluation of a mother-infant-pair model called “Umoyo”, which was designed to be low cost and scalable in a public health system. Facilities with the Umoyo model dedicate a clinic day to provide services to only HIV-exposed-infants (HEIs) and their mothers. Such models are in operation with reported success in Zambia but have not been rigorously tested. This work establishes whether the Umoyo model would improve 12-month retention of HEIs. Methods A cluster randomized trial including 28 facilities was conducted across two provinces of Zambia to investigate the impact on 12-month retention of HEIs in care. These facilities were offering prevention of mother to child transmission (PMTCT) services and supported by the same implementing partner. Randomization was achieved by use of the covariate constrained optimization technique. Secondary outcomes included the impact of Umoyo clinics on social support and perceived HIV stigma among mothers. For each of the outcomes, a difference-in-difference analysis was conducted at the facility level using the unweighted t-test. Results From 13 control (12-month retention at endline: 45%) and 11 intervention facilities (12-month retention at endline: 33%), it was found that Umoyo clinics had no impact on 12-month retention of HEIs in the t-test (-11%; 99% CI: -40.1%, 17.2%). Regarding social support and stigma, the un-weighted t-test showed no impact though sensitivity tests showed that Umoyo had an impact on increasing social support (0.31; 99% CI: 0.08, 0.54) and reducing perceived stigma from health care workers (-0.27: 99% CI: -0.46, -0.08). Conclusion The Umoyo approach of having a dedicated clinic day for HEIs and their mothers did not improve retention of HEIs though there are indications that it can increase social support among mothers and reduce stigma. Without further support to the underlying health system, based on the evidence generated through this evaluation, the Umoyo clinic day approach on its own is not considered an effective intervention to increase retention of HIV-exposed infants.

The Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents with Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3121-3121
Author(s):  
Alexander Claviez ◽  
Markus Tiemann ◽  
Heike Lueders ◽  
Reza Parwaresch ◽  
Guenther Schellong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Children And Adolescents ◽  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Barr Virus ◽  
Ebv Infection ◽  
Nodular Sclerosis ◽  
Epstein Barr ◽  
The Impact

Abstract The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin’s lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available due to small series. 842 children and adolescents (55% male) with a median age of 13.7 years (range, 2–20) from consecutive pediatric DAL/GPOH multicenter treatment studies HD-90 and HD-95 were studied for the presence of latent EBV infection in Hodgkin and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Histology subtypes were as follows: nodular sclerosis (NSHL) 549, mixed cellularity (MCHL) 190, lymphocyte predominance (NLPHL) 90, lymphocyte depletion (LDHL) 6, lymphocyte-rich classical HL (LRCHL) 5, not specified 2. 88 patients had stage I, 470 had stage II, 172 had stage III and 112 had stage IV. B symptoms were present in 274 patients (33%). LMP status was compared with clinical parameters and established risk factors. A total of 263 patients (32%) were LMP positive. EBV infection correlated with gender (male 39% vs. female 23%; p<.001), histological subtype (MCHL 69% vs. NSHL 22% vs. NLPHL 6%; p<.001) and age (<10 years 67% vs ≥10 years 28%, p<.001. With a median follow-up of 4.9 years (0.3–12) 820 patients (97%) are alive. Probability of overall survival at 10 years (±SD) for EBV negative and positive patients was 98±1% and 95±1%, respectively (p=.017 by log-rank test). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89±2% and 84±4%, respectively (p=.86). With respect to LMP status, a negative effect of latent EBV infection on overall survival became evident only for patients treated for advanced stages (p=.003), those with nodular sclerosis subtype Bennett II (p=.02) and B symptoms (p=.05). In a multivariate regression analysis, allocation to treatment group (RR=3.7) and LMP positivity (RR=3.01) were independent factors for overall survival and presence of B symptoms (RR=2.4) for FFS. Under current highly effective polychemotherapy with or without involved field radiotherapy in pediatric HL, latent EBV infection has no influence on FFS in univariate and multivariate analysis. LMP positivity, however, seems to be associated with an inferior overall survival in some subgroups.

The Impact of Epstein Bar Virus On Hodgkin Lymphoma's Histopathological Patterns in Morocco

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4781-4781
Author(s):  
Soumaya Anoun ◽  
Sofia Marouane ◽  
Meryem Kabbali ◽  
Soumia Zamiati ◽  
Said Benchekroun ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Developed Countries ◽  
Histological Subtype ◽  
Male Predominance ◽  
Barr Virus ◽  
Ebv Infection ◽  
Hematoxylin Staining ◽  
Staining Protocol ◽  
Epstein Barr ◽  
The Impact

Abstract Abstract 4781 Background: In Morocco, improvement of living conditions and access to healthcare has increased life expectancy from 58 years in 1980 to 72 years in 2010. There has been a corresponding decrease in early childhood infections, including Epstein Barr virus (EBV) infection, which is associated with Hodgkin lymphoma (HL). Mixed cellularity (MC) was the most common histopathological subset of HL in Morocco. Prior studies have shown the shift to nodular sclerosis (NS) subset since 1998. Currently, the incidence of NS subtype is still predominant in our country. Our aim is to study the incidence of EBV infection in HL Moroccan population and correlate its decrease to explain the shift of HL histopathological pattern. Patients and methods: We compared children and adults with HL diagnosed during 3 periods: 1980–1995, 1998–2005 and 2010–2011 in the same university medical centre. All histological samples were prepared for examination by paraffin method, than stained by Hematoxylin staining protocol. Immunuhistochemical features of Hodgkin Reed Sternberg cells were performed to assess the expression of antibodies markers (CD30, CD15). The EBV profiling was identified by immunohistochemical stains for EBV latent membrane protein 1 (LMP-1) for the last periods. Statistical comparison of all the features was performed by Epi Info software. Results: The features of 1200 HL patients were enrolled. The average number of HL cases per year was 46 patients for the first period versus 74 patients for the last period. The mean age was respectively 24 years (range 2–64 years) for the first period, 32 years (range 2–60 years) for the second period and 34 years (range 3–76 years) for the third one. Sex-Ratio showed male predominance. The comparison of HL incidence through the age over the past 30 years is further characterized by a significant higher incidence in elderly patients (2% versus 10%), and lower incidence in young children (32% versus 7%). The expression of LMP1 in HRS is significantly reduced between the two last periods (P=0.001). LMP1 positivity is higher in patients under fifteen years than in young adults. Currently, NS is the most prevalent histological subtype with a significant increasing frequency through the three periods (p< 0.001) instead of MC subtype. (Table1). Conclusion: HL pattern in Morocco tends to be like in developed countries. The shift of HL histological subtype from CM to NS could be explained by the decrease of EBV infection in Hodgkin Reed Sternberg cells. More patients need to be enrolled to confirm this hypothesis Disclosures: No relevant conflicts of interest to declare.

scholarly journals Modulation of alternative splicing during early infection of human primary B lymphocytes with Epstein-Barr virus (EBV): a novel function for the viral EBNA-LP protein

2021 ◽  
Vol 49 (18) ◽  
pp. 10657-10676
Author(s):  
Evelyne Manet ◽  
Hélène Polvèche ◽  
Fabrice Mure ◽  
Paulina Mrozek-Gorska ◽  
Florian Roisné-Hamelin ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
B Lymphocytes ◽  
Splice Variant ◽  
Epstein Barr Virus ◽  
Human Herpesvirus ◽  
Splicing Regulation ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
The Impact

Abstract Epstein-Barr virus (EBV) is a human herpesvirus associated with human cancers worldwide. Ex vivo, the virus efficiently infects resting human B lymphocytes and induces their continuous proliferation. This process is accompanied by a global reprogramming of cellular gene transcription. However, very little is known on the impact of EBV infection on the regulation of alternative splicing, a pivotal mechanism that plays an essential role in cell fate determination and is often deregulated in cancer. In this study, we have developed a systematic time-resolved analysis of cellular mRNA splice variant expression during EBV infection of resting B lymphocytes. Our results reveal that major modifications of alternative splice variant expression appear as early as day 1 post-infection and suggest that splicing regulation provides—besides transcription—an additional mechanism of gene expression regulation at the onset of B cell activation and proliferation. We also report a role for the viral proteins, EBNA2 and EBNA-LP, in the modulation of specific alternative splicing events and reveal a previously unknown function for EBNA-LP—together with the RBM4 splicing factor—in the alternative splicing regulation of two important modulators of cell proliferation and apoptosis respectively, NUMB and BCL-X.

scholarly journals Postnatal Cytomegalovirus Exposure in Infants of Antiretroviral-Treated and Untreated HIV-Infected Mothers

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Sarah A. Meyer ◽  
Daniel J. Westreich ◽  
Emily Patel ◽  
Elizabeth P. Ehlinger ◽  
Linda Kalilani ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Postnatal Growth ◽  
Hiv Exposed Infants ◽  
Breastfed Infants ◽  
Postnatal Transmission ◽  
Growth Faltering ◽  
Hiv Exposed ◽  
The Impact ◽  
The Relationship ◽  
Hiv 1

HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4–6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log10rise CMV load per log10rise HIV-1 RNA load, 95% CI 0.13–0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (−0.53, 95% CI: −0.96, −0.10) and weight-for-age (−0.40, 95% CI: −0.67, −0.13)Z-score at six months in exposed, uninfected infants. As the impact of maternal antiretroviral therapy on the magnitude of postnatal CMV exposure may be limited, our findings of an inverse relationship between infant growth and milk CMV load highlight the importance of defining the role of perinatal CMV exposure on growth faltering of HIV-exposed infants.

scholarly journals Maternal Epstein-Barr Virus-Specific Antibodies and Risk of Infection in Ugandan Infants

2020 ◽  
Author(s):  
Rana Minab ◽  
Wei Bu ◽  
Hanh Nguyen ◽  
Abigail Wall ◽  
Anton M Sholukh ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Epstein Barr Virus ◽  
Maternal Antibody ◽  
Adcc Activity ◽  
Viral Neutralization ◽  
Barr Virus ◽  
Ebv Infection ◽  
Maternal Hiv ◽  
Epstein Barr ◽  
Hiv Exposed

Abstract Background Epstein-Barr virus (EBV) infection is a major cause of malignancy worldwide. Maternal antibody is thought to prevent EBV infection because it is uncommon in early infancy. Maternal HIV infection is associated with an increased incidence of EBV infection in exposed infants, which we hypothesized results from impaired transfer of EBV-neutralizing maternal antibodies. Methods Among Ugandan infants followed for EBV acquisition from birth, we measured antibody binding to EBV glycoproteins (gp350, gH/gL) involved in B-cell and epithelial-cell entry, as well as viral neutralization and antibody-dependent cellular cytotoxicity (ADCC) activity in plasma samples prior to infection. These serologic data were analyzed for differences between HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) infants, and for associations with incident infant EBV infection. Results HEU infants had significantly higher titers than HUU infants for all EBV-binding and neutralizing antibodies measured (P &lt; .01) but not ADCC activity, which was similar between groups. No antibody measure was associated with a decreased risk of EBV acquisition in the cohort. Conclusions Our findings indicate that in this cohort maternal antibody did not protect infants against EBV infection through viral neutralization. The identification of protective nonneutralizing antibody functions would be invaluable for the development of an EBV vaccine.

scholarly journals The influence of human genetic variation on Epstein–Barr virus sequence diversity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sina Rüeger ◽  
◽  
Christian Hammer ◽  
Alexis Loetscher ◽  
Paul J. McLaren ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Epstein Barr Virus ◽  
Rare Variants ◽  
Amino Acid Level ◽  
Genomic Variation ◽  
Human Genetic Variation ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
The Impact

AbstractEpstein–Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4 + T cell count < 200/mm3 and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level (BRLF1:p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.

Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host

Blood ◽  
2004 ◽  
Vol 104 (5) ◽  
pp. 1482-1489 ◽  
Author(s):  
Pierre Rivailler ◽  
Angela Carville ◽  
Amitinder Kaur ◽  
Pasupuleti Rao ◽  
Carol Quink ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Rhesus Macaques ◽  
Humoral Response ◽  
Lymphoproliferative Disease ◽  
Barr Virus ◽  
Ebv Infection ◽  
Oral Inoculation ◽  
Epstein Barr ◽  
Intravenous Inoculation ◽  
Specific Humoral Response

Abstract To develop a model for Epstein-Barr virus (EBV) pathogenesis in immunosuppressed hosts, we studied experimental infections of immunocompetent versus SHIV 89.6P–infected, immunosuppressed rhesus macaques with the EBV-related rhesus lymphocryptovirus (LCV). Primary LCV infection after oral inoculation of 4 immunocompetent animals was characterized by an acute viremia and seroconversion followed by asymptomatic LCV persistence. Four immunosuppressed macaques infected orally with LCV failed to develop an LCV-specific humoral response and viremia was more pronounced, but there was no evidence of LCV-induced lymphoproliferative disease. A more aggressive primary challenge was administered by intravenous inoculation of 108 autologous, LCV-immortalized B cells in 4 additional immunosuppressed animals. Two animals with modest immunosuppression remained asymptomatic, and 1 of 2 severely immunosuppressed animals developed an aggressive, monoclonal LCV-positive lymphoma. These studies demonstrate the potential for lymphomagenesis in an experimental model system for EBV infection and underscore the strength and depth of immune control in limiting LCV-induced lymphoproliferative disease.

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