The Immunomodulatory Capacity of an Epstein-Barr Virus Abortive Lytic Cycle: Potential Contribution to Viral Tumorigenesis

Sánchez, Alejandra Consuelo; Fuentes‐Pananá, Ezequiel M.

doi:10.3390/cancers10040098

Cited by 42 publications

(50 citation statements)

References 171 publications

(197 reference statements)

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“…The B cell version of multicentric Castleman’s disease is a KSHV-associated lymphoproliferative neoplasm that is also characterized by lytic KSHV replication [89]. The role of lytic replication is not as well established for EBV-related tumors, but reports have been emerging describing the presence of lytic EBV cells in EBV tumors, and the oncogenic functions of EBV lytic proteins [90,91]. The contribution of lytic replication in EBV infection has been more extensively explored in connection with nasopharyngeal carcinoma.…”

Section: Cases In Which Viral Replication Is Required For Oncogenesismentioning

confidence: 99%

More than just oncogenes: mechanisms of tumorigenesis by human viruses

Gaglia

Münger

2018

Current Opinion in Virology

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Most humans are infected with at least one of the known human cancer viruses during their lifetimes. While the initial infection with these viruses does not cause major disease, infected cells can acquire cancer hallmarks, particularly upon immunosuppression or exposure to co-carcinogenic stimuli. Even though cancer formation represents a rare outcome of a viral infection, approximately one out of eight human cancers has a viral etiology. Viral cancers present unique opportunities for prophylaxis, diagnosis, and therapy, as demonstrated by the success of HBV and HPV vaccines and HCV antivirals in decreasing the incidence of tumors that are caused by these viruses. Here we review common characteristics and mechanisms of action of the human oncogenic viruses.

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Section: Cases In Which Viral Replication Is Required For Oncogenesismentioning

confidence: 99%

More than just oncogenes: mechanisms of tumorigenesis by human viruses

Gaglia

Münger

2018

Current Opinion in Virology

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“…The role of the lytic EBV proteins was highlighted in some recent reviews [13,14]. Overall, the authors clearly demonstrated the role of these lytic EBV proteins in tumorigenesis.…”

Section: The Role Of Some Lytic Ebv Proteins In the Tumorigenesis Andmentioning

confidence: 92%

“…EBV lytic infection may increase the total number of latently infected cells by enhancing transmission of the virus from cell to cell and thus constitutes an essential aspect of viral pathogenesis. A small subset of lytically infected cells was detected in biopsies of EBV-associated malignancies [13,[17][18][19][20][21][22], suggesting a potential role of viral lytic infection in promoting tumor growth in vivo. Furthermore, several studies have indicated that the viral lytic cycle in a fraction of B cells promotes the transformation of B lymphocytes in vitro [23] and growth of B-cell lymphoma in vivo [24,25] through the release of paracrine growth factors and angiogenic factors [26].…”

Section: Arguments Of the Pathogenic Role Of Lytic Infection In Ebv-amentioning

confidence: 99%

“…In the absence of other lytic genes, particularly those encoding late structural proteins, without the formation of infective viral particles, BZLF1 expression is termed the "abortive lytic cycle" (Figure 4) [13]. The existence of abortive cycles was demonstrated in EBV-associated malignancies through the detection of either the ZEBRA protein (via monoclonal antibodies) or mRNA: Hodgkin disease [17], Non-Hodgkin lymphoma (NHL) [18,88], NPC [20], or Burkitt lymphoma [21].…”

Section: Evidence Of Abortive Lytic Cycle and Their Role In Tumorigenmentioning

confidence: 99%

“…Importantly however, EBV (as other gammaherpesviruses, e.g., KSHV) can also undergo abortive lytic reactivation, resulting in the expression of early lytic genes without subsequent virion assembly and cell lysis [13]. Although numerous efforts to understand these disorders' molecular basis have focused on viral latency, EBV lytic cycles are now widely accepted as major contributors to oncogenesis and could be important targets in the development of new therapeutic or diagnostic approaches [14,15].…”

Section: Introductionmentioning

confidence: 99%

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The Role of the Epstein-Barr Virus Lytic Cycle in Tumor Progression: Consequences in Diagnosis and Therapy

Drouet¹

2020

Human Herpesvirus Infection - Biological Features, Transmission, Symptoms, Diagnosis and Treatment

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The Epstein-Barr virus (EBV) reactivation corresponds to the activation of EBV global replication involving not only the origin of the latent viral replication but also that of the origin of lytic replication. During this reactivation, a minority of B cells infected with EBV in its latent form enter the lytic phase. During this phase, all EBV proteins are produced, enabling the assembly of complete virions that lysate their host cells and infect neighboring cells (lytic cycle). This horizontal EBV transmission seeks to increase the pool of EBV-infected B cells. This chapter seeks to review the role of the lytic EBV proteins (particularly that of the ZEBRA protein) in tumor development. This protein is the main transcription factor of EBV, expressed during the activation of the lytic cycle. Recently, we demonstrated that this immediate early protein can be detected in the soluble state (s-ZEBRA) in the serum of patients with posttransplant lymphoproliferative disorder. We highlighted the role of ZEBRA in EBV pathogenesis in transplanted subjects, not only as a key protein in the activation of EBV replication but also as a protein "toxoid" released into the extracellular milieu. This release could result in increased secretion of immunomodulatory cytokines and that of angiogenesis-promoting factors conducive to tumor progression.

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Follow‐up of renal transplant recipients after acute COVID‐19—A prospective cohort single‐center study

Jukić

Jurić

Furić-Čunko

et al. 2021

Immunity Inflam & Disease

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Introduction Although most patients recover within several weeks after acute COVID‐19, some of them develop long‐lasting clinical symptoms. Renal transplant recipients have an increased mortality risk from COVID‐19. We aimed to describe complications occurring after COVID‐19 in this group of patients. Methods A prospective single‐center cohort study was conducted at University Hospital Centre Zagreb. Patients with two negative reverse transcriptase‐polymerase chain reaction (RT‐PCR) tests for SARS‐CoV‐2 after COVID‐19 were eligible for further follow‐up at our outpatient clinic. They underwent detailed clinical and laboratory assessments. The primary outcome was the development of complications after COVID‐19. Results Only 11.53% of renal transplant recipients who survived acute COVID‐19 were symptomless and free from new‐onset laboratory abnormalities during the median follow‐up of 64 days (range: 50–76 days). Three patients died from sepsis after discharge from the hospital. In 47 patients (45.2%), clinical complications were present, while 74 patients (71.2%) had one or more laboratory abnormalities. The most common clinical complications included shortness of breath (19.2%), tiredness (11.5%), peripheral neuropathy (7.7%), self‐reported cognitive impairments (5.7%), and dry cough (7.7%). Most common laboratory abnormalities included shortened activated partial thromboplastin time (50%), elevated D‐dimers (36.5%), elevated fibrinogen (30.16%), and hypogammaglobulinemia (24%). Positive RT‐PCR for cytomegalovirus (8.7%), Epstein–Barr virus (26%), or BK virus (16.3%). Multivariate analysis identified the history of diabetes mellitus and eGFR CKD‐EPI as predictors for the development of post‐COVID clinical complications. Six months after acute COVID‐19, elevated D‐dimers persisted with normalization of other laboratory parameters. Twenty‐nine patients were hospitalized, mostly with several concomitant problems. However, initially reported clinical problems gradually improved in the majority of patients. Conclusion Post‐COVID‐19 clinical and laboratory complications are frequent in the renal transplant population, in some of them associated with significant morbidity. All patients recovered from acute COVID‐19 should undergo long‐term monitoring for evaluation and treatment of complications.

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The Immunomodulatory Capacity of an Epstein-Barr Virus Abortive Lytic Cycle: Potential Contribution to Viral Tumorigenesis

Cited by 42 publications

References 171 publications

More than just oncogenes: mechanisms of tumorigenesis by human viruses

More than just oncogenes: mechanisms of tumorigenesis by human viruses

The Role of the Epstein-Barr Virus Lytic Cycle in Tumor Progression: Consequences in Diagnosis and Therapy

Follow‐up of renal transplant recipients after acute COVID‐19—A prospective cohort single‐center study

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