JC Polyomavirus, progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome: a review

Abstract

The human neurotropic virus JC Polyomavirus, a member of the Polyomaviridae family, is the opportunistic infectious agent causing progressive multifocal leukoencephalopathy, typically in immunocompromised individuals. The spectrum of underlying reasons for the systemic immunosuppression that permits JCV infection in the central nervous system has evolved over the past 2 decades, and therapeutic immunosuppression arousing JCV infection in the brain has become increasingly prominent as a trigger for PML. Effective immune restoration subsequent to human immunodeficiency virus-related suppression is now recognized as a cause for unexpected deterioration of symptoms in patients with PML, secondary to a rebound inflammatory phenomenon called immune reconstitution inflammatory syndrome, resulting in significantly increased morbidity and mortality in a disease already infamous for its lethality. This review addresses current knowledge regarding JC Polyomavirus, progressive multifocal leukoencephalopathy, progressive multifocal leukoencephalopathy-related immune reconstitution inflammatory syndrome, and the immunocompromised states that incite JC Polyomavirus central nervous system infection, and discusses prospects for the future management of these conditions.

Fatal JC-virus Granular Cerebellar Neuronopathy associated with Autoimmune Lymphoproliferative Syndrome and Common Variable Immunodeficiency

“…JCV CSF quanti cation as a surrogate marker for treatment response is debated, and PCR methods are not standardized. However, overall there seems to be reasonable correlation between CSF-JCV levels and clinical treatment response (24,25).…”

Use of Pembrolizumab for Treatment of Progressive Multifocal Leukoencephalopathy in People Living with HIV

“…IRIS occurs in about 4–42% of HIV/AIDS patients starting cART [ 6 , 18 , 19 ] and is the result of an excessive immune response to either pre-existing or latent opportunistic pathogens [ 20 ]. PML has been reported to occur within the first weeks to months after initiating cART and has been associated with clinical and radiological worsening [ 21 , 22 ]. In patient 3, we observed, about four weeks after starting cART, a neurological decline and appearance at MRI of contrast enhancement, oedema and mass effect, compatible with a diagnosis of unmasked PML.…”

The Role of Extracellular Vesicles in Demyelination of the Central Nervous System

“…JCV, a nonenveloped double-stranded DNA virus that belongs to the Polyomaviridae family [138], is a widespread opportunistic human pathogen which infects more than 70% of the population. JCV infection is asymptomatic and frequently occurs early in life, establishing latency in several cell types and organs such as the brain, tonsils, lungs, B lymphocytes and kidneys [139]. Under certain poorly understood circumstances, usually accompanied by host immunosuppression, the virus may spread to the CNS, crossing the BBB and reactivating to cause PML.…”

“…Under certain poorly understood circumstances, usually accompanied by host immunosuppression, the virus may spread to the CNS, crossing the BBB and reactivating to cause PML. Thus, latent JCV, termed the "archetype" form that is incapable of productively infecting glial cells [140], may transform into the neurotropic "prototype" form, which may in turn infect OLs and cause CNS disease [139]. Within the CNS, JCV infects OLs and astrocytes and induces demyelination.…”