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Biomedicines Jul 2023Infectious agents can pose a significant challenge in kidney transplantation, as they have the potential to cause direct infections in the transplanted kidney. These... (Review)
Review
Infectious agents can pose a significant challenge in kidney transplantation, as they have the potential to cause direct infections in the transplanted kidney. These infections can lead to a decline in kidney function and reduce the longevity of the transplanted kidney. Common post-transplant allograft infections include bacterial pyelonephritis and the BK virus infection, while adenovirus, JC virus, and cytomegalovirus are less frequent but can also lead to significant allograft dysfunctions. The histopathological features of these infections are characterized by the infiltration of inflammatory cells in the kidney interstitial area and the presence of viral nuclear inclusions or cytopathic changes in the renal tubular epithelial cells. The confirmation of causative organisms can be achieved by immunohistochemical staining or the visualization of viral particles using electron microscopic examination. However, these methods typically require a longer turnaround time and are not readily available in developing countries, unlike standard hematoxylin-eosin staining. Notably, the differential diagnosis of interstitial inflammation in kidney allografts almost always includes T cell-mediated rejection, which has a different treatment approach than allograft infections. The aim of this review was to prompt clinicians to identify diverse pathological alterations as observed in kidney allograft biopsies, thereby facilitating further investigations and the management of suspected kidney allograft infections.
PubMed: 37509541
DOI: 10.3390/biomedicines11071902 -
International Journal of Molecular... Apr 2017Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are... (Review)
Review
Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses. Until now, there has not been a clear strategy that should be followed to avoid PML risk and in parallel reduce clinical and radiological rebound activity. In this review, we analyzed the results of clinical trials and case reports in relation to the following situations: natalizumab continuation, natalizumab discontinuation followed by full therapeutic suspension or switch to other first or second line MS treatments. Quitting all MS treatment after natalizumab increases MS activity occurrence. The results regarding the therapeutic switch are not homogeneous, so at the moment there are no established guidelines regarding natalizumab treatment after 24 administrations; the choice is currently based on the professional experience of the neurologist, and on patients' clinical features and preferences.
Topics: Adrenal Cortex Hormones; Animals; Antibodies, Monoclonal; Humans; Immunologic Factors; JC Virus; Leukoencephalopathy, Progressive Multifocal; Multiple Sclerosis; Natalizumab
PubMed: 28468254
DOI: 10.3390/ijms18050940 -
Viruses May 2022JC polyomavirus (JCPyV) is a small non-enveloped virus that establishes lifelong, persistent infection in most of the adult population. Immune-competent patients are... (Review)
Review
JC polyomavirus (JCPyV) is a small non-enveloped virus that establishes lifelong, persistent infection in most of the adult population. Immune-competent patients are generally asymptomatic, but immune-compromised and immune-suppressed patients are at risk for the neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Studies with purified JCPyV found it undergoes receptor-dependent infectious entry requiring both lactoseries tetrasaccharide C (LSTc) attachment and 5-hydroxytryptamine type 2 entry receptors. Subsequent work discovered the major targets of JCPyV infection in the central nervous system (oligodendrocytes and astrocytes) do not express the required attachment receptor at detectable levels, virus could not bind these cells in tissue sections, and viral quasi-species harboring recurrent mutations in the binding pocket for attachment. While several research groups found evidence JCPyV can use novel receptors for infection, it was also discovered that extracellular vesicles (EVs) can mediate receptor independent JCPyV infection. Recent work also found JCPyV associated EVs include both exosomes and secretory autophagosomes. EVs effectively present a means of immune evasion and increased tissue tropism that complicates viral studies and anti-viral therapeutics. This review focuses on JCPyV infection mechanisms and EV associated and outlines key areas of study necessary to understand the interplay between virus and extracellular vesicles.
Topics: Astrocytes; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Neurodegenerative Diseases; Polyomavirus Infections
PubMed: 35746603
DOI: 10.3390/v14061130 -
Reviews in Medical Virology Mar 2016Progressive multifocal leukoencephalopathy (PML) is a devastating and often fatal demyelinating disease of the central nervous system for which effective therapies are... (Review)
Review
Progressive multifocal leukoencephalopathy (PML) is a devastating and often fatal demyelinating disease of the central nervous system for which effective therapies are lacking. It is caused by the replication of polyomavirus JC (JCV) in the oligodendrocytes and astrocytes leading to their cytolytic death and loss of myelin from the subcortical white matter. While the virus is very common in human populations worldwide, the incidence of the disease is very low and confined almost exclusively to individuals with some form of immunological dysfunction. However, the number of people who constitute the at-risk population is growing larger and includes individuals with HIV-1/AIDS and patients receiving immunomodulatory therapies such as multiple sclerosis patients treated with natalizumab. Further adding to the public health significance of this disease are the difficulties encountered in the diagnosis of PML and the lack of useful biomarkers for PML progression. In this review, we examine the diagnostic assays that are available for different aspects of the JCV life cycle, their usefulness and drawbacks, and the prospects for improvements.
Topics: Acquired Immunodeficiency Syndrome; Antibodies, Viral; Astrocytes; Biomarkers; Central Nervous System; Humans; Immunocompromised Host; JC Virus; Leukoencephalopathy, Progressive Multifocal; Oligodendroglia; RNA, Viral; Viral Load
PubMed: 26663440
DOI: 10.1002/rmv.1866 -
Journal of Neurovirology Dec 2015The high prevalence of asymptomatic JC polyomavirus (JCV) infection in the general population indicates coexistence with the human host and efficient immune control in... (Review)
Review
The high prevalence of asymptomatic JC polyomavirus (JCV) infection in the general population indicates coexistence with the human host and efficient immune control in healthy individuals. For unknown reasons, kidney-resident archetypic JCV strains can turn into neurotropic JCV strains which in hereditary or acquired states of immunodeficiency cause opportunistic infection and cytolytic destruction of glial cells or granule cell neurons resulting in progressive multifocal demyelination in the central nervous system (CNS) or cerebellar atrophy, respectively. Immunomodulatory or immunosuppressive therapies with specific monoclonal antibodies including natalizumab, efalizumab, and rituximab have increased the risk of progressive multifocal leukoencephalopathy (PML) among treated patients, highlighting that symptomatic JCV infection of the CNS is associated with disturbances of adaptive immunity affecting B cells, antibodies, and CD4(+) and/or CD8(+) T cells. To date, no specific therapy to overcome PML is available and the only way to eliminate the virus from the CNS is to reconstitute global immune function. However, since the identification of JCV as the causative agent of PML 40 years ago, it is still not fully understood which components of the immune system prevent the development of PML and which immune mechanisms are involved in eliminating the virus from the CNS. This review gives an update about adaptive JCV-specific immune responses.
Topics: Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal
PubMed: 25740538
DOI: 10.1007/s13365-014-0294-y -
Current Opinion in Nephrology and... Jan 2019The presence of viruses in urine (urine virome) typically reflects infection in the kidneys and urinary tract. The urinary virome is associated with HIV-associated... (Review)
Review
PURPOSE OF REVIEW
The presence of viruses in urine (urine virome) typically reflects infection in the kidneys and urinary tract. The urinary virome is associated with HIV-associated nephropathy and chronic glomerulosclerosis. There are many associations of this microbiome with human diseases that remain to be described. This manuscript reviews emerging data on relationships between kidney disease and urinary tract infection/colonization with JC polyomavirus (JCPyV).
RECENT FINDINGS
Approximately 30% of the adult population sheds JCPyV in the urine. Further, urinary tract infection with one polyomavirus strain appears to inhibit secondary infections. The presence of urinary JCPyV and BK polyomavirus (BKPyV) replication were measured with polymerase chain reaction in African Americans to assess relationships with apolipoprotein L1 gene (APOL1)-associated nephropathy. Urinary JCPyV was associated with paradoxically lower rates of nephropathy in those with APOL1 high-risk genotypes. Subsequent studies revealed African Americans with JCPyV viruria had lower rates of nondiabetic nephropathy independent from APOL1.
SUMMARY
Urinary tract JCPyV replication is common and associates with lower rates of nephropathy. This relationship is observed in diverse settings. Results support a host immune system that fails to eradicate nonnephropathic viruses and is also less likely to manifest renal parenchymal inflammation resulting in glomerulosclerosis.
Topics: Apolipoprotein L1; Humans; JC Virus; Kidney Diseases; Urinary Tract Infections; Urine; Virus Replication
PubMed: 30320619
DOI: 10.1097/MNH.0000000000000464 -
Viruses Sep 2020Polyomavirus infection is widespread in the human population. This family of viruses normally maintains latent infection within the host cell but can cause a range of... (Review)
Review
Polyomavirus infection is widespread in the human population. This family of viruses normally maintains latent infection within the host cell but can cause a range of human pathologies, especially in immunocompromised individuals. Among several known pathogenic human polyomaviruses, JC polyomavirus (JCPyV) has the potential to cause the demyelinating disease progressive multifocal leukoencephalopathy (PML); BK polyomavirus (BKPyV) can cause nephropathy in kidney transplant recipients, and Merkel cell polyomavirus (MCPyV) is associated with a highly aggressive form of skin cancer, Merkel cell carcinoma (MCC). While the mechanisms by which these viruses give rise to the relevant diseases are not well understood, it is clear that the control of gene expression in each polyomavirus plays an important role in determining the infectious tropism of the virus as well as their potential to promote disease progression. In this review, we discuss the mechanisms governing the transcriptional regulation of these pathogenic human polyomaviruses in addition to the best-studied simian vacuolating virus 40 (SV40). We highlight the roles of viral -acting DNA elements, encoded proteins and miRNAs that control the viral gene expression. We will also underline the cellular transcription factors and epigenetic modifications that regulate the gene expression of these viruses.
Topics: BK Virus; Carcinoma, Merkel Cell; Gene Expression Regulation, Viral; Humans; JC Virus; Latent Infection; Leukoencephalopathy, Progressive Multifocal; Merkel cell polyomavirus; Polyomavirus; Polyomavirus Infections; Simian virus 40; Tumor Virus Infections
PubMed: 32987952
DOI: 10.3390/v12101072 -
Tidsskrift For Den Norske Laegeforening... Dec 2017Progressive multifocal leukoencephalopathy is a rare, opportunistic infection of the central nervous system caused by the John Cunningham virus (JCV). There is no... (Review)
Review
Progressive multifocal leukoencephalopathy is a rare, opportunistic infection of the central nervous system caused by the John Cunningham virus (JCV). There is no effective antiviral treatment available, and restoring immunocompetence is essential for survival. If this occurs too quickly, however, the inflammatory response may prove fatal. This is an up-to-date review of the disorder, intended for clinicians responsible for immunomodulatory therapy.
Topics: Aged; Female; Humans; Immunologic Factors; JC Virus; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Male; Middle Aged; Tomography, X-Ray Computed
PubMed: 29231623
DOI: 10.4045/tidsskr.16.1092 -
Neuropsychiatric Disease and Treatment 2017Natalizumab is a monoclonal antibody that acts as an α4 integrin antagonist to prevent leukocyte trafficking into the central nervous system. It is US Food and Drug... (Review)
Review
Natalizumab is a monoclonal antibody that acts as an α4 integrin antagonist to prevent leukocyte trafficking into the central nervous system. It is US Food and Drug Administration (FDA) approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Natalizumab demonstrated high efficacy in Phase III trials by reducing the annualized relapse rate, preventing multiple sclerosis (MS) lesion accumulation on magnetic resonance imaging, and decreasing the probability of sustained progression of disability. The leading safety concern with natalizumab is its association with progressive multifocal leukoencephalopathy (PML), a rare brain infection typically seen only in severely immunocompromised patients caused by reactivation of the John Cunningham virus (JCV). Careful analysis of risk factors for PML in natalizumab-treated MS patients, specifi-cally the presence of anti-JCV antibodies, has led to risk mitigation strategies to improve safety. Additional biomarkers are under investigation to further aid risk stratification. Natalizumab's high efficacy and favorable tolerability profile have led to a broad use by MS physicians, as both first-and second-line treatments. This review discusses the natalizumab efficacy, safety, and tolerability and finishes with pragmatic considerations regarding its use in clinical practice.
PubMed: 28721050
DOI: 10.2147/NDT.S114636