Novel syndromes associated with JC virus infection of neurons and meningeal cells

Abstract

Purpose of review The availability of a growing number of immunomodulatory medications over the past few years has been associated with various JC Virus (JCV) associated brain syndromes in patients with autoimmune diseases, including multiple sclerosis, Crohn’s disease and psoriasis which had not been previously recognized as predisposing factors for progressive multifocal leukoencephalopathy (PML). This review covers the three novel syndromes discovered in the last decade which are caused by JCV infection of neurons and meningeal cells. Recent findings For more than 30 years, JCV was thought to exclusively infect oligodendrocytes and astrocytes in the white matter of the brain of immunosuppressed individuals. We now recognize that JCV-infected glial cells are frequently located at the gray-white matter junction or exclusively within the gray matter causing demyelination in the cortex. Mutations in JCV can trigger a change in tropism leading to involvement of other cell types, such as neurons and meningeal cells, causing clinically distinct entities. These new features of JCV infection provide challenges for clinicians taking care of affected patients and investigators studying the biology of this polyomavirus, its pathogenesis, and tropism. Summary We hope that increasing awareness of these syndromes will lead to early diagnosis, and pave the way for new avenues of research to better understand all aspects of JCV pathogenesis and develop efficient therapies for our patients. However, we need to remain vigilant and open to the possibility that additional JC variants or yet unknown polyomaviruses may be associated with neurological diseases as well.

Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: a decade of lessons learned

“…Infection of the neurons in granular cell layer in the cerebellum can also result in a symptomatic neuronopathy. 22 For cells to be susceptible to JCV infection, they need to express DNA binding proteins that recognize the viral genome, non-coding control region (NCCR) that initiates viral DNA replication and transcription for RNA and eventually protein synthesis (Figure 1steps 6,7/ Table 1). There are a number of such transcription factors that are critical to JCV multiplication.…”

In Vitro and In Vivo Models for the Study of Human Polyomavirus Infection

“…JCPyV causes PML in immunocompromised patients, such as patients with HIV/AIDS, hematological malignancies and in patients receiving immunomodulatory medication, such as integrin very late antigen-4 (VLA-4) monoclonal antibody (natalizumab, Tysabri ® ), leukocyte function associated antigen 1 (LFA-1) monoclonal antibody (efalizumab, Raptiva ® ) and CD20 monoclonal antibody (rituximab, MabThera ® ) for the treatment of multiple sclerosis, Crohn’s disease, lymphoma, severe forms of plaque-type psoriasis and rheumatic diseases [58]. In addition to PML, JCPyV can cause other neurological disorders, such as JCPyV granule cell neuronopathy, JCPyV encephalopathy and meningitis [59]. …”

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

“…JCV affects the white matter of the brain by productive and lytic infection of oligodendrocytes and astrocytes. However, in 2003 a rare syndrome caused by productive and selective infection of cerebellar granule cell neurons by a JCV variant with a small deletion in the VP1 capsid was described (1)(2)(3).…”