Clearance of Circulating Epstein‐Barr Virus DNA in Children with Acute Malaria after Antimalaria Treatment

Donati, Daria; Espmark, Eva; Kironde, Fred; Mbidde, Edward; Kamya, Moses R.; Lundkvist, Åke; Wahlgren, Mats; Bejarano, Maria Teresa; Falk, Kerstin I.

doi:10.1086/500839

Cited by 73 publications

(83 citation statements)

References 32 publications

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“…[18] Several studies have described viral reactivation during prolonged stress events among immunocompetent patients. [5,19,20] EBV reactivation has also been found to be associated with several autoimmune or cardiovascular diseases such as gastritis, rheumatoid arthritis, lupus, and multiple sclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, it has been associated with stress among draftees and astronauts or even during malaria infection in children. [3][4][5] Furthermore, several in vitro and in vivo investigations have highlighted a relationship between CMV infection and EBV reactivation, suggesting possible synergic pathogenicity. [6][7][8] CMV can also impair the immune response to EBV during aging.…”

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confidence: 99%

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Epstein-Barr virus reactivation in critically ill immunocompetent patients

et al. 2015

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O ver the past years, particular attention has been given to herpes virus reactivations among immunocompetent critically ill patients. Although the true pathogenicity of these reactivations is still debated, some authors have hypothesized that it could be related to specific immune failure caused by sepsis or multi-organ failure. Others have argued that it is only a marker of severity. There is increasing evidence that reactivation of cytomegalovirus (CMV) and herpes simplex virus (HSV) is associated with mortality or morbidity, mainly for ventilator-acquired pneumonia. [1,2] CMV seroprevalence ranges from 40% to 95% depending on several factors, including age and geographic area. HSV1 seroprevalence is around 65% among the French population. Epstein-Barr virus (EBV) reactivation has been well docu- Original Article Epstein-Barr Virus Reactivation in Critically IllImmunocompetent Patients Background: Herpes viruses can be reactivated among immunocompetent patients in intensive care unit (ICU). Cytomegalovirus (CMV) and herpes simplex virus (HSV) have been the most studied. We hypothesized that Epstein-Barr virus (EBV) could also be reactivated in immunocompetent patients during their stay in ICU and that this would be associated with morbidity and mortality. Methods:This prospective observational study included 90 patients with an ICU stay of ≥ 5 days. CMV and HSV were considered when clinically suspected and DNA was researched in blood or bronchoalveolar lavage (BAL). EBV DNA viral quantification was performed in the blood samples. Results:EBV DNA was detected in blood of 61 patients (median length for positivity of 7.5 days). CMV DNA was detected in blood of 16 patients (median length for positivity of 13.5 days) and BAL of 6 patients. HSV1 DNA was detected in the BAL of 28 patients (median length for positivity of 7.5 days). Nineteen patients had no viral reactivation, 1 experienced only CMV, 32 had only EBV, 5 had only HSV, 6 had EBV and CMV, 14 had EBV and HSV, and 9 patients reactivated three viruses. Mortality was higher among patients with EBV reactivation (33/61 vs. 7/25, p = 0.02). Length of stay (21 vs. 10 days, p < 0.001) and length of mechanical ventilation (15 vs. 7 days, p < 0.001) were higher among patients with EBV reactivation. Conclusions: This study shows that EBV DNA is detected in blood of diverse ICU patients with ≥ ≥ 5 days of stay and that it is associated with morbidity and mortality. Larger dynamic prospective studies are needed to correlate viral reactivation with immune system evolution during ICU stay and to determine the role of polyviral reactivations. (Biomed J 2015;38:70-76)

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Section: Discussionmentioning

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Epstein-Barr virus reactivation in critically ill immunocompetent patients

et al. 2015

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“…EBV persists in a latent state in resting memory B cells that circulate in the peripheral blood (Thorley-Lawson 2001). The exposure of B cells to malarial antigens during multiple infectious episodes could reactivate the virus from memory B cells, thereby increasing viral load and the number of EBV-infected cells (Donati et al 2006;Chene et al 2007).…”

Section: Epidemiology Of Ebl: the Role Of Infectious Agents In The Pamentioning

confidence: 99%

Oncogenic Mechanisms in Burkitt Lymphoma

Schmitz

Ceribelli

Pittaluga

et al. 2014

Cold Spring Harbor Perspectives in Medicine

213

174

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Burkitt lymphoma is a germinal center B-cell-derived cancer that was instrumental in the identification of MYC as an important human oncogene more than three decades ago. Recently, new genomics technologies have uncovered several additional oncogenic mechanisms that cooperate with MYC to create this highly aggressive cancer. The transcription factor TCF-3 is central to Burkitt lymphoma pathogenesis. TCF-3 is rendered constitutively active in Burkitt lymphoma by two related mechanisms: (1) somatic mutations that inactivate its negative regulator ID3, and (2) somatic mutations in TCF-3 that block the ability of ID3 to bind and interfere with its activity as a transcription factor. TCF-3 is also a master regulator of normal germinal center B-cell differentiation. Within the germinal center, TCF-3 up-regulates genes that are characteristically expressed in the rapidly dividing centroblasts, the putative cell of origin for Burkitt lymphoma, while repressing genes expressed in the less proliferative centrocytes. TCF-3 promotes antigen-independent (tonic) B-cell-receptor signaling in Burkitt lymphoma by transactivating immunoglobulin heavy-and light-chain genes while repressing PTPN6, which encodes the phosphatase SHP-1, a negative regulator of Bcell-receptor signaling. Tonic B-cell-receptor signaling sustains Burkitt lymphoma survival by engaging the PI3 kinase pathway. In addition, TCF-3 promotes cell-cycle progression by transactivating CCND3, encoding a D-type cyclin that regulates the G 1 -S phase transition. Additionally, CCND3 accumulates oncogenic mutations that stabilize cyclin D3 protein expression and drive proliferation. These new insights into Burkitt lymphoma pathogenesis suggest new therapeutic strategies, which are sorely needed in developing regions of the world where this cancer is endemic.

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“…More recently, an age-related deficiency in IFN-␥ recall responses to EBV lytic and latent antigens was demonstrated in children (i.e., 5 to 9 years of age) with ho-loendemic malaria exposure compared to those from an area of malaria hypoendemicity (23). In addition, EBV load in African children correlates with malaria exposure (24,25), further implicating coinfection as a risk factor for eBL tumorigenesis. However, it remains unclear how P. falciparum malaria might potentiate a deficit in EBV-specific T-cell immunity and thus contribute to eBL lymphomagenesis.…”

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confidence: 99%

Holoendemic Malaria Exposure Is Associated with Altered Epstein-Barr Virus-Specific CD8 ⁺ T-Cell Differentiation

Chattopadhyay

Chelimo

Embury

et al. 2013

J Virol

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e Coinfection with Plasmodium falciparum malaria and Epstein-Barr virus (EBV) is a major risk factor for endemic Burkitt lymphoma (eBL), still one of the most prevalent pediatric cancers in equatorial Africa. Although malaria infection has been associated with immunosuppression, the precise mechanisms that contribute to EBV-associated lymphomagenesis remain unclear. In this study, we used polychromatic flow cytometry to characterize CD8 ؉ T-cell subsets specific for EBV-derived lytic (BMFL1 and BRLF1) and latent (LMP1, LMP2, and EBNA3C) antigens in individuals with divergent malaria exposure. No malaria-associated differences in EBV-specific CD8 ؉ T-cell frequencies were observed. However, based on a multidimensional analysis of CD45RO, CD27, CCR7, CD127, CD57, and PD-1 expression, we found that individuals living in regions with intense and perennial (holoendemic) malaria transmission harbored more differentiated EBV-specific CD8 ؉ T-cell populations that contained fewer central memory cells than individuals living in regions with little or no (hypoendemic) malaria. This profile shift was most marked for EBV-specific CD8؉ T-cell populations that targeted latent antigens. Importantly, malaria exposure did not skew the phenotypic properties of either cytomegalovirus (CMV)-specific CD8 ؉ T cells or the global CD8 ؉ memory T-cell pool. These observations define a malaria-associated aberration localized to the EBV-specific CD8 ؉ T-cell compartment that illuminates the etiology of eBL.

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Clearance of Circulating Epstein‐Barr Virus DNA in Children with Acute Malaria after Antimalaria Treatment

Cited by 73 publications

References 32 publications

Epstein-Barr virus reactivation in critically ill immunocompetent patients

Epstein-Barr virus reactivation in critically ill immunocompetent patients

Oncogenic Mechanisms in Burkitt Lymphoma

Holoendemic Malaria Exposure Is Associated with Altered Epstein-Barr Virus-Specific CD8 ⁺ T-Cell Differentiation

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Clearance of Circulating Epstein‐Barr Virus DNA in Children with Acute Malaria after Antimalaria Treatment

Cited by 73 publications

References 32 publications

Epstein-Barr virus reactivation in critically ill immunocompetent patients

Epstein-Barr virus reactivation in critically ill immunocompetent patients

Oncogenic Mechanisms in Burkitt Lymphoma

Holoendemic Malaria Exposure Is Associated with Altered Epstein-Barr Virus-Specific CD8 + T-Cell Differentiation

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Holoendemic Malaria Exposure Is Associated with Altered Epstein-Barr Virus-Specific CD8 ⁺ T-Cell Differentiation