Host-Immune Interactions in JC Virus Reactivation and Development of Progressive Multifocal Leukoencephalopathy (PML)

Khalili, Arash; Craigie, Michael; Donadoni, Martina; Sariyer, Ilker Kudret

doi:10.1007/s11481-019-09877-8

Cited by 12 publications

(11 citation statements)

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“…There is now a hypothesis that four essential conditions related to the development of the JCV-associated PML are as follows: (a) a significant immunosuppression (b) recombination in viral promoter allowing efficient transcription and replication in permissive cells (c) presence of cellular host factors to interact with the viral promoter in permissive cells d) and the ability of the virus to cross the blood–brain barrier. Since JCV reactivation often occurs in immunocompromised patients, it has been proposed that the host immune system (especially cell-mediated immunity) plays an incredible role in controlling the JCV by preventing its reactivation and PML development [ 25 ]. Although the exact immunological and non-immunological mechanism of JCV reactivation is not clear, detailed studies have been conducted to assess some intracellular elements' impact on JCV regulation.…”

Section: Discussionmentioning

confidence: 99%

“…It seems that the BK and JC viruses have different mechanisms of reactivation and shedding. Although the role of immunosuppression in the onset of virus replication and shedding in urine has been controversial, immunosuppression is a prerequisite for JCV viremia [ 25 ]. The same event occurs about BKV replication and shedding in plasma as well [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

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Determining host factors contributing to the reactivation of JC virus in kidney transplant recipients

Keykhosravi

Khosravi

Shenagari

et al. 2022

Virol J

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Background and aims The John Cunningham virus (JCV) is the established etiological agent of the polyomavirus-associated nephropathy among renal transplant recipients. In the present study, we aimed to determine the probable predictive factors leading to JCV replication in renal transplant patients. Material and methods Urine and plasma samples were collected from a total of 120 consecutive renal‐transplanted patients without preliminary screening from Jan 2018 to Mar 2019. After DNA extraction, the simultaneous detection and quantification of JCV and BK polyomavirus (BKV) were conducted using a Real-time quantitative PCR method. Moreover, statistical analyses were performed using the statistical software packages, SPSS version 21. Results The prevalence of JCV viruria and viremia among renal transplant recipients were 26 (21.67%) and 20 (16.67%), respectively. A significant association was observed between the JCV and two risk factors, diabetes mellitus (P = 0.002) and renal stones (P = 0.015). The prevalence of JCV viremia among recipients who were grafted near time to sampling was significantly higher (P = 0.02). There was a statistically significant coexistence between BK and JC viruses among our patients (P = 0.029). The frequency of JCV viruria in males was reported almost three times more than in females (P = 0.005). The JCV shedding in urine was significantly associated with the tropical steroids like prednisolone acetate, which have been the standard regimen (P = 0.039). Multivariable analysis revealed duration of post-transplantation (OR, 0.89; P = 0.038), diabetes mellitus (OR, 1.85; P = 0.034), and renal stone (OR 1.10; P = 0.04) as independent risk factors associated with JCV viremia post-renal transplantation. Conclusion It seems that the discovery of potential risk factors, including immunological and non-immunological elements, may offer a possible preventive or therapeutic approach in the JCV disease episodes. The results of this study may also help clarify the probable clinical risk factors involving in progressive multifocal leukoencephalopathy development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Determining host factors contributing to the reactivation of JC virus in kidney transplant recipients

Keykhosravi

Khosravi

Shenagari

et al. 2022

Virol J

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“…Mechanisms of JCV reactivation and consecutive development of PML are just partly understood ( 10 ). Impaired viral control due to alterations in lymphocytes – either by reduction of absolute lymphocyte counts or impaired lymphocytic function – are assumed ( 11 , 12 ).…”

Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy associated with chemotherapy induced lymphocytopenia in solid tumors – case report of an underestimated complication

et al. 2022

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BackgroundJC virus reactivation causing progressive multifocal leukoencephalopathy (PML) occurs preferentially in human immunodeficiency virus (HIV) positive individuals or patients suffering from hematologic neoplasms due to impaired viral control. Reactivation in patients suffering from solid malignancies is rarely described in published literature.Case PresentationHere we describe a case of PML in a male patient suffering from esophageal cancer who underwent neoadjuvant radiochemotherapy and surgical resection in curative intent resulting in complete tumor remission. The radiochemotherapy regimen contained carboplatin and paclitaxel (CROSS protocol). Since therapy onset, the patient presented with persistent and progredient leukopenia and lymphopenia in absence of otherwise known risk factors for PML. Symptom onset, which comprised aphasia, word finding disorder, and paresis, was apparent 7 months after therapy initiation. There was no relief in symptoms despite standard of care PML directed supportive therapy. The patient died two months after therapy onset.ConclusionPML is a very rare event in solid tumors without obvious states of immununosuppression and thus harbors the risk of unawareness. The reported patient suffered from lymphopenia, associated with systemic therapy, but was an otherwise immunocompetent individual. In case of neurologic impairment in patients suffering from leukopenia, PML must be considered – even in the absence of hematologic neoplasia or HIV infection.

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“…A decrease in naive CD4 þ cells was also found in one of them. Indeed, apart from low CD4 þ cell count, the impact of immunosuppressive factors on JCV regulation and reactivation is not well known [32,36]. For example, the occurrence of PML in patients treated with ruxolitinib, a selective Janus kinase inhibitor, despite normal CD4 þ T-cell count, or in patients treated with natalizumab, a humanized IgG4 antibody that does not affect CD4 þ T-cell count, suggests the involvement of other immunological factors [37,38].…”

Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy in patients with immunovirological control and at least 6 months of combination antiretroviral therapy

Dalla-Pozza¹,

Hentzien²,

Allavena³

et al. 2021

Aids

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Bani-Sadr a,k , and the Dat'AIDS study group Objectives and methods: Progressive multifocal leukoencephalopathy (PML) has rarely been reported in people with HIV (PWH) with long-term HIV immune-virological control. We describe the clinical and biological characteristics of patients with confirmed PML among PWH with a CD4 þ cell count more than 200 cells/ml and an undetectable HIV RNA viral load after at least 6 months of combined antiretroviral therapy (cART) at the time of PML diagnosis, in the large French multicenter Dat'AIDS cohort.Results: Among 571 diagnoses of PML reported in the Dat'AIDS cohort between 2000 and 2019, 10 cases (1.75%) occurred in PWH with a CD4 þ cell count greater than 200 cells/ml and an undetectable HIV RNA viral load after at least 6 months of cART. Median CD4 þ cell count at PML diagnosis was 395 cells/ml . The median duration between the last detectable HIV viral load and the PML diagnosis was 41.1 months (IQR 8.2-67.4). Only one patient treated with rituximab-based chemotherapy for a large B-cell lymphoma had an established risk factor for PML. Among the nine other patients with no apparent severe immunodeficiency, multiple factors of impaired immunity could have led to the development of PML: hepatitis C virus (HCV) co-infection (n ¼ 6), cirrhosis (n ¼ 4), HHV-8 co-infection (n ¼ 3) with Kaposi's sarcoma (n ¼ 2) in association with Castleman's disease (n ¼ 1) and indolent IgA multiple myeloma (n ¼ 1). Conclusion:This study highlights that factors other than low CD4 þ cell count and high HIV viral load may be associated with the occurrence of PML. Further studies are warranted to investigate in greater detail the immunologic characteristics of PWH with immune-virological control who develop PML.

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Host-Immune Interactions in JC Virus Reactivation and Development of Progressive Multifocal Leukoencephalopathy (PML)

Cited by 12 publications

References 121 publications

Determining host factors contributing to the reactivation of JC virus in kidney transplant recipients

Determining host factors contributing to the reactivation of JC virus in kidney transplant recipients

Progressive multifocal leukoencephalopathy associated with chemotherapy induced lymphocytopenia in solid tumors – case report of an underestimated complication

Progressive multifocal leukoencephalopathy in patients with immunovirological control and at least 6 months of combination antiretroviral therapy

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