Host-Immune Interactions in JC Virus Reactivation and Development of Progressive Multifocal Leukoencephalopathy (PML). 2019

Amir Khalili, and Michael Craigie, and Martina Donadoni, and Ilker Kudret Sariyer
Department of Neuroscience and Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, Medical Education and Research Building, 7th Floor, Philadelphia, PA, 19140, USA.

With the advent of immunomodulatory therapies and the HIV epidemic, the impact of JC Virus (JCV) on the public health system has grown significantly due to the increased incidence of Progressive Multifocal Leukoencephalopathy (PML). Currently, there are no pharmaceutical agents targeting JCV infection for the treatment and the prevention of viral reactivation leading to the development of PML. As JCV primarily reactivates in immunocompromised patients, it is proposed that the immune system (mainly the cellular-immunity component) plays a key role in the regulation of JCV to prevent productive infection and PML development. However, the exact mechanism of JCV immune regulation and reactivation is not well understood. Likewise, the impact of host factors on JCV regulation and reactivation is another understudied area. Here we discuss the current literature on host factor-mediated and immune factor-mediated regulation of JCV gene expression with the purpose of developing a model of the factors that are bypassed during JCV reactivation, and thus are potential targets for the development of therapeutic interventions to suppress PML initiation. Graphical Abstract.

UI MeSH Term Description Entries
D007167 Immunotherapy Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. Immunotherapies
D007577 JC Virus A species of POLYOMAVIRUS, originally isolated from the brain of a patient with progressive multifocal leukoencephalopathy. The patient's initials J.C. gave the virus its name. Infection is not accompanied by any apparent illness but serious demyelinating disease can appear later, probably following reactivation of latent virus. Human Polyomavirus JC,JC polyomavirus,Polyomavirus, JC,John Cunningham Virus,Polyomavirus hominis 2,Polyomavirus JC, Human,Virus, John Cunningham
D007968 Leukoencephalopathy, Progressive Multifocal An opportunistic viral infection of the central nervous system associated with conditions that impair cell-mediated immunity (e.g., ACQUIRED IMMUNODEFICIENCY SYNDROME and other IMMUNOLOGIC DEFICIENCY SYNDROMES; HEMATOLOGIC NEOPLASMS; IMMUNOSUPPRESSION; and COLLAGEN DISEASES). The causative organism is JC Polyomavirus (JC VIRUS) which primarily affects oligodendrocytes, resulting in multiple areas of demyelination. Clinical manifestations include DEMENTIA; ATAXIA; visual disturbances; and other focal neurologic deficits, generally progressing to a vegetative state within 6 months. (From Joynt, Clinical Neurology, 1996, Ch26, pp36-7) Encephalitis, JC Polyomavirus,Progressive Multifocal Leukoencephalopathy,JC Polyomavirus Encephalopathy,Encephalopathies, JC Polyomavirus,Encephalopathy, JC Polyomavirus,JC Polyomavirus Encephalitis,Leukoencephalopathies, Progressive Multifocal,Multifocal Leukoencephalopathies, Progressive,Multifocal Leukoencephalopathy, Progressive,Progressive Multifocal Leukoencephalopathies
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000076662 Host Microbial Interactions Interactions between a host and microbe or microbiota. Host-Bacteria Interactions,Host-Microbe Interactions,Host-Microbial Interactions,Host-Virus Interactions,Microbe-Host Interactions,Microbial-Host Interactions,Microbiota-Host Interactions,Virus-Host Interactions,Bacteria Host Interactions,Bacterial-Host Interactions,Bacterium-Host Interactions,Host Bacteria Interactions,Host Microbe Interactions,Host Microbiota Interactions,Host Virus Interactions,Host-Fungal Interactions,Host-Microbial Interface,Microbe Host Interactions,Microbial Host Interactions,Microbiota Host Interactions,Viral-Host Interactions,Virus Host Interactions,Bacteria Host Interaction,Bacterial Host Interactions,Bacterial-Host Interaction,Bacterium Host Interactions,Bacterium-Host Interaction,Host Bacteria Interaction,Host Fungal Interactions,Host Microbe Interaction,Host Microbial Interaction,Host Microbial Interface,Host Microbiota Interaction,Host Virus Interaction,Host-Bacteria Interaction,Host-Fungal Interaction,Host-Microbe Interaction,Host-Microbial Interaction,Host-Microbial Interfaces,Host-Virus Interaction,Interaction, Host-Bacteria,Interaction, Host-Microbe,Interaction, Host-Microbial,Interaction, Host-Virus,Interaction, Microbe-Host,Interaction, Microbial-Host,Interaction, Microbiota-Host,Interaction, Virus-Host,Interactions, Host-Bacteria,Interactions, Host-Microbe,Interactions, Host-Microbial,Interactions, Host-Virus,Interactions, Microbe-Host,Interactions, Microbial-Host,Interactions, Microbiota-Host,Interactions, Virus-Host,Microbe Host Interaction,Microbe-Host Interaction,Microbial Host Interaction,Microbial-Host Interaction,Microbiota Host Interaction,Microbiota-Host Interaction,Viral Host Interactions,Viral-Host Interaction,Virus Host Interaction,Virus-Host Interaction
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014775 Virus Activation The mechanism by which latent viruses, such as genetically transmitted tumor viruses (PROVIRUSES) or PROPHAGES of lysogenic bacteria, are induced to replicate and then released as infectious viruses. It may be effected by various endogenous and exogenous stimuli, including B-cell LIPOPOLYSACCHARIDES, glucocorticoid hormones, halogenated pyrimidines, IONIZING RADIATION, ultraviolet light, and superinfecting viruses. Prophage Excision,Prophage Induction,Virus Induction,Viral Activation,Activation, Viral,Activation, Virus,Activations, Viral,Activations, Virus,Excision, Prophage,Excisions, Prophage,Induction, Prophage,Induction, Virus,Inductions, Prophage,Inductions, Virus,Prophage Excisions,Prophage Inductions,Viral Activations,Virus Activations,Virus Inductions
D016867 Immunocompromised Host A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Immunosuppressed Host,Immunocompromised Patient,Host, Immunocompromised,Host, Immunosuppressed,Hosts, Immunocompromised,Hosts, Immunosuppressed,Immunocompromised Hosts,Immunocompromised Patients,Immunosuppressed Hosts,Patient, Immunocompromised,Patients, Immunocompromised

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