Cellular normalization of viral DNA loads on whole blood improves the clinical management of cytomegalovirus or Epstein Barr virus infections in the setting of pre‐emptive therapy

Bressollette-Bodin, Céline; Coste‐Burel, Marianne; Besse, Bernard; André-Garnier, Élisabeth; Ferré, Virginie; Imbert-Marcille, Berthe-Marie

doi:10.1002/jmv.21334

Cited by 28 publications

(26 citation statements)

References 29 publications

(30 reference statements)

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“…iLC and mLC populations derived from the progenitor cells of four different donors were exposed to BAC4 at an MOI of 10 PFU/cell for 15 min, 1 h, or 4 h. At each time point, cells were collected, washed, and stored (untreated) or washed and treated with citrate buffer for 1 min at room temperature or with proteinase K for 1 h at 4°C. After additional washes, cells were pelleted and subjected to real-time quantitative PCR with primers hybridizing to the viral UL122/123 ORF (79) or to the cellular albumin gene (63) and the number of viral genomes/cell was calculated.…”

Section: Resultsmentioning

confidence: 99%

Human Cytomegalovirus Infection of Langerhans-Type Dendritic Cells Does Not Require the Presence of the gH/gL/UL128-131A Complex and Is Blocked after Nuclear Deposition of Viral Genomes in Immature Cells

Lauron¹,

Yü

Hertel³

2014

J Virol

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bHuman cytomegalovirus (CMV) enters its host via the oral and genital mucosae. Langerhans-type dendritic cells (LC) are the most abundant innate immune cells at these sites, where they constitute a first line of defense against a variety of pathogens. We previously showed that immature LC (iLC) are remarkably resistant to CMV infection, while mature LC (mLC) are more permissive, particularly when exposed to clinical-strain-like strains of CMV, which display a pentameric complex consisting of the viral glycoproteins gH, gL, UL128, UL130, and UL131A on their envelope. This complex was recently shown to be required for the infection of immature monocyte-derived dendritic cells. We thus sought to establish if the presence of this complex is also necessary for virion penetration of LC and if defects in entry might be the source of iLC resistance to CMV. Here we report that the efficiency of LC infection is reduced, but not completely abolished, in the absence of the pentameric complex. While virion penetration and nuclear deposition of viral genomes are not impaired in iLC, the transcription of the viral immediate early genes UL122 and UL123 and of the delayed early gene UL50 is substantially lower than that in mLC. Together, these data show that the UL128, UL130, and UL131A proteins are dispensable for CMV entry into LC and that progression of the viral cycle in iLC is restricted at the step of viral gene expression.

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Section: Resultsmentioning

confidence: 99%

Human Cytomegalovirus Infection of Langerhans-Type Dendritic Cells Does Not Require the Presence of the gH/gL/UL128-131A Complex and Is Blocked after Nuclear Deposition of Viral Genomes in Immature Cells

Lauron¹,

Yü

Hertel³

2014

J Virol

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“…12,13 Briefly, CMV (US6 gene), EBV (BNRF1gene) and HHV6 (U65-U66 gene) DNA were quantified on 5 ml DNA extracts and viral loads were expressed as the number of viral DNA copies/ml of blood. Detection limit of the three PCR ranged from 5 to 10 viral genome copies per assay and samples with viral loads over 2 log/ml of blood were considered as positive.…”

Section: Methodsmentioning

confidence: 99%

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Chevallier

Hebia-Fellah²,

Planche

et al. 2009

Bone Marrow Transplant

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Occurrence of CMV, EBV and human herpes virus 6 (HHV6) infections and immune reconstitution were compared in 15 adult patients receiving a cord blood transplantation (CBT) and 40 patients who received an allogeneic transplantation from a matched unrelated donor (MUD). Herpes virus DNA quantifications in the blood (459 samples) were performed before and then monthly up to 9 months after transplant and the main lymphocytes populations were counted at 3, 6 and 9 months. Incidence of HHV6 infection was significantly higher in the CBT group (80 vs 42.5%; Po0.0001), with higher viral load (Po0.0001). In multivariate analysis, the use of a CBT and a myeloablative conditioning regimen were found to increase the risk of HHV6 infection (odds ratio (OR) ¼ 5.4, P ¼ 0.02 and OR ¼ 3.5, P ¼ 0.04, respectively). Incidences of CMV were similar between the two groups whereas MUD increased the risk of EBV infection, in univariate analysis only. HHV6 reactivation translated toward delayed neutrophils and plts engraftment in the two groups. MUD and CBT do not share the same immune reconstitution patterns, notably for B and CD8 lymphocytes and NK cells. There is a strong and specific relationship between HHV6 infection and the use of cord blood cells.

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“…DNA quantifications were performed using real-time PCR procedures, as previously described. 29 Briefly, EBV (BNRF1 gene) was quantified on 5 ml DNA extracts and viral loads were expressed as the number of viral DNA copies. EBV reactivation was defined as any EBV PCR load above 1000 copies of EBV DNA/10 5 cells.…”

Section: Ebv Monitoring and Therapymentioning

confidence: 99%

Features of Epstein-Barr Virus (EBV) reactivation after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation

et al. 2011

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This single centre study assessed the incidence, kinetics and predictive factors of Epstein-Barr Virus (EBV) reactivation and EBV-related lymphoproliferative diseases (LPDs) in 175 consecutive patients who received a reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cumulative incidence of EBV reactivation at 6 months after allo-HSCT defined as an EBV PCR load above 1000 copies of EBV DNA/10 5 cells was 15%, and none of these patients experienced any sign or symptom of LPD. A total of 17 patients, who had EBV DNA levels exceeding 1000 copies/10 5 cells on two or more occasions, were pre-emptively treated with rituximab. With a median follow-up of 655 (range, 92-1542) days post allo-HSCT, there was no statistically significant difference in term of outcome between those patients who experienced an EBV reactivation and those who did not. In multivariate analysis, the use of antithymocyte globulin as part of the RIC regimen was the only independent risk factor associated with EBV reactivation (relative risk ¼ 4.9; 95% confidence interval, 1.1-21.0; P ¼ 0.03). We conclude that patients undergoing RIC allo-HSCT using anti-thymocyte globulin as part of the preparative regimen are at higher risk for EBV reactivation. However, this did not impact on outcome, as quantitative monitoring of EBV viral load by PCR and preemptive rituximab therapy allowed for significantly reducing the risk of EBV-related LPD.

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Cellular normalization of viral DNA loads on whole blood improves the clinical management of cytomegalovirus or Epstein Barr virus infections in the setting of pre‐emptive therapy

Cited by 28 publications

References 29 publications

Human Cytomegalovirus Infection of Langerhans-Type Dendritic Cells Does Not Require the Presence of the gH/gL/UL128-131A Complex and Is Blocked after Nuclear Deposition of Viral Genomes in Immature Cells

Human Cytomegalovirus Infection of Langerhans-Type Dendritic Cells Does Not Require the Presence of the gH/gL/UL128-131A Complex and Is Blocked after Nuclear Deposition of Viral Genomes in Immature Cells

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Features of Epstein-Barr Virus (EBV) reactivation after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation

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