Epstein-Barr Virus load and immune activation in Human Immunodeficiency Virus type 1-infected patients

Petrara, Maria Raffaella; Cattelan, Anna María; Zanchetta, Marisa; Sasset, Lolita; Freguja, Riccardo; Gianesin, Ketty; Cecchetto, Maria Grazia; Carmona, Francesco; Rossi, Anita De

doi:10.1016/j.jcv.2011.12.013

Cited by 52 publications

(49 citation statements)

References 34 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, HIV-infected patients with high levels of EBV present higher levels of pro-inflammatory cytokines (IL-6, IL-10, TNF-α) and PAMPs (LPS, 16S rDNA) than patients with low EBV levels. EBV load is also closely correlated with the percentage of activated B cells [47]. Although these findings deal with EBV dynamics in HIV-infected patients, the concept that B-cell activation may favor expansion of EBV-infected B cells can also be applied to the context of immunosuppression associated with transplantation ( Fig.…”

Section: Mechanisms For Ebv-driven Ptldmentioning

confidence: 96%

Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment

et al. 2015

Self Cite

View full text Add to dashboard Cite

Post-transplant lymphoproliferative disorders (PTLDs) represent the most severe complication of both solid organ and hematopoietic stem cell transplantation. The Epstein-Barr Virus (EBV) is the main driver of PTLD, particularly those occurring early after transplantation. EBV-driven malignancies are associated with selective expression of latent viral proteins, but uncontrolled lytic replication may favor early phases of cell transformation. Besides immunodepression, persistent immune activation and chronic inflammation play an important role in both virus reactivation and expansion of EBV-infected B cells. EBV-induced immortalization requires the expression of telomerase. TERT, the rate-limiting component of the telomerase complex, is central in the switch from the lytic to the latent viral program, and TERT inhibition induces the EBV lytic cycle and cell death. Immunotherapy and combination of EBV lytic cycle inducers with antiviral drugs are promising strategies to improve the treatment of PTLD patients. This review is aimed at providing an update on the intriguing association between EBV and PTLD, mainly focusing on cases arising after kidney and liver transplantation, which account for the vast majority of transplants.

show abstract

Section: Mechanisms For Ebv-driven Ptldmentioning

confidence: 96%

Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…One striking finding of this study is that there are significant correlations between the levels of antigenstimulated cIL-10 production in PBMC and RhCMV genome copy numbers detected in saliva. This is not unique to RhCMV, as cIL-10 levels have been positively associated, either alone or with other biomarkers, with increased burdens of other pathogens, including human papillomavirus, HIV, hepatitis B virus, EpsteinBarr virus (EBV), Mycobacterium tuberculosis, Leishmania spp., dengue virus, and murine and human CMV (45,(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72). While the specific cell type(s) responsible for elevated cIL-10 expression in response to RhCMV antigen exposure was not explored, multiple cell types have been implicated for other pathogens, including regulatory B and T cells.…”

Section: Discussionmentioning

confidence: 99%

Exploitation of Interleukin-10 (IL-10) Signaling Pathways: Alternate Roles of Viral and Cellular IL-10 in Rhesus Cytomegalovirus Infection

Eberhardt

Deshpande

Fike

et al. 2016

J Virol

View full text Add to dashboard Cite

There is accumulating evidence that the viral interleukin-10 (vIL-10) ortholog of both human and rhesus cytomegalovirus (HCMV and RhCMV, respectively) suppresses the functionality of cell types that are critical to contain virus dissemination and help shape long-term immunity during the earliest virus-host interactions. In particular, exposure of macrophages, peripheral blood mononuclear cells, monocyte-derived dendritic cells, and plasmacytoid dendritic cells to vIL-10 suppresses multiple effector functions including, notably, those that link innate and adaptive immune responses. Further, vaccination of RhCMV-uninfected rhesus macaques with nonfunctional forms of RhCMV vIL-10 greatly restricted parameters of RhCMV infection following RhCMV challenge of the vaccinees. Vaccinees exhibited significantly reduced shedding of RhCMV in saliva and urine following RhCMV challenge compared to shedding in unvaccinated controls. Based on the evidence that vIL-10 is critical during acute infection, the role of vIL-10 during persistent infection was analyzed in rhesus macaques infected long term with RhCMV to determine whether postinfection vaccination against vIL-10 could change the virus-host balance. RhCMV-seropositive macaques, which shed RhCMV in saliva, were vaccinated with nonfunctional RhCMV vIL-10, and shedding levels of RhCMV in saliva were evaluated. Following robust increases in vIL-10-binding and vIL-10-neutralizing antibodies, shedding levels of RhCMV modestly declined, consistent with the interpretation that vIL-10 may play a functional role during persistent infection. However, a more significant association was observed between the levels of cellular IL-10 secreted in peripheral blood mononuclear cells exposed to RhCMV antigens and shedding of RhCMV in saliva. This result implies that RhCMV persistence is associated with the induction of cellular IL-10 receptor-mediated signaling pathways. IMPORTANCEHuman health is adversely impacted by viruses that establish lifelong infections that are often accompanied with increased morbidity and mortality (e.g., infections with HIV, hepatitis C virus, or human cytomegalovirus). A longstanding but unfulfilled goal has been to develop postinfection vaccine strategies that could "reboot" the immune system of an infected individual in ways that would enable the infected host to develop immune responses that clear reservoirs of persistent virus infection, effectively curing the host of infection. This concept was evaluated in rhesus macaques infected long term with rhesus cytomegalovirus by repeatedly immunizing infected animals with nonfunctional versions of the rhesus cytomegalovirus-encoded viral interleukin-10 immune-modulating protein. Following vaccine-mediated boosting of antibody titers to viral interleukin-10, there was modest evidence for increased immunological control of the virus following vaccination. More significantly, data were also obtained that indicated that rhesus cytomegalovirus is able to persist due to upregulation of the cellular interleukin-...

show abstract

“…It has previously been demonstrated that peripheral blood EBv viral load may be persistently high in HIv-infected patients without accompanying clinical signs or symptoms of EBv-linked disease [8][9][10]. Regardless of peripheral CD4 cell depletion, chronic immune activation in HIv-infected patients may play a role in B-cell stimulation, expansion of EBv-infected cells and persistent EBv replication [23]. The high EBv viral load observed in HIv-infected patients with reactive hemophagocytic syndrome may therefore be an epiphenomenon associated with the chronic HIv infection.…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr virus viral load in human immunodeficiency virus-positive patients with reactive hemophagocytic syndrome

Boisseau

Lambotte

Galicier

et al. 2015

Infectious Diseases

View full text Add to dashboard Cite

Because human immunodeficiency virus (HIV)-infected patients control Epstein-Barr virus (EBV) replication poorly, we hypothesized that reactive hemophagocytic syndrome (HS) in these patients may be associated with poor control of EBV. The files of 314 patients with a suspected diagnosis of HS were retrospectively reviewed. EBV viral load at the time of HS was compared between HIV-positive and -negative patients. A confirmed diagnosis of HS was made in 162 patients [109 males, median age 48 (35-62) years]. Among them, 61 (38%) were HIV positive [median HIV viral load 3.2 (1.6-5.5) log/ml, median CD4 count 94 (28-190)/mm(3)]. The median EBV viral load was significantly higher in HIV-positive than in HIV-negative patients [4.0 (2.9-4.6) vs 2.5 (0-4.2) log/ml, p = 0.002]. It was higher both in patients with hematological malignancy-associated HS [4.0 (2.9-4.4) vs 2.9 (0-4.9) log/ml, p = 0.03] and in patients with infection-associated HS [3.9 (0-4.9) vs 0 (0-4.1) log/ml, p = 0.14]. However, EBV viral load was not significantly higher in HIV-infected patients with confirmed HS than in HIV-infected patients for whom HS was unlikely [4.0 (2.9-4.6) vs 3.9 (2.6-4.1) log/ml, p = 0.48].The high EBV viral load observed in HIV-infected patients with HS may be more likely to reflect the chronic HIV infection than to be the direct trigger of HS.

show abstract

Epstein-Barr Virus load and immune activation in Human Immunodeficiency Virus type 1-infected patients

Cited by 52 publications

References 34 publications

Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment

Post-transplant lymphoproliferative disorders: From epidemiology to pathogenesis-driven treatment

Exploitation of Interleukin-10 (IL-10) Signaling Pathways: Alternate Roles of Viral and Cellular IL-10 in Rhesus Cytomegalovirus Infection

Epstein–Barr virus viral load in human immunodeficiency virus-positive patients with reactive hemophagocytic syndrome

Contact Info

Product

Resources

About