What is the JC (John Cunningham) virus?

From the Guidelines

The JC virus (John Cunningham virus) is a common polyomavirus that infects approximately 70-90% of the global population, typically during childhood or early adulthood, and can reactivate in individuals with weakened immune systems to cause a serious brain infection called Progressive Multifocal Leukoencephalopathy (PML) 1.

Key Characteristics of the JC Virus

• The virus remains dormant in the kidneys, bone marrow, and lymphoid tissue in most people, without causing symptoms.
• Reactivation of the virus can occur in individuals with weakened immune systems, such as those with HIV/AIDS, organ transplant recipients, or patients taking certain immunosuppressive medications like natalizumab (Tysabri) 1.
• PML destroys the myelin sheath covering nerve cells, leading to symptoms such as weakness, vision problems, impaired speech, and cognitive difficulties.

Risk Assessment and Monitoring

• Regular monitoring for JC virus antibodies may be recommended for patients on immunosuppressive therapy to assess risk, with the anti-JCV antibody index used to stratify patients according to their risk of developing PML during treatment with natalizumab 1.
• Patients with an anti-JCV antibody index >1.5 are considered to require high-frequency MRI monitoring to mitigate their risk of developing PML, while those with an anti-JCV antibody index ≤1.5 require moderate-frequency MRI monitoring.

Management and Treatment

• There is no specific treatment for JC virus infection, so management focuses on restoring immune function when possible and providing supportive care.
• The risks and benefits of treatment should be re-evaluated at appropriate intervals, which will be determined by the patient’s disease course and wishes 1.

From the FDA Drug Label

TYSABRI increases your chance (risk) of getting a rare brain infection that usually leads to death or severe disability. This infection is called progressive multifocal leukoencephalopathy (PML). ... have been infected by the John Cunningham Virus (JCV). JCV is a common virus that is harmless in most people but can cause PML in people who have weakened immune systems, such as people taking TYSABRI.

1. 1 Progressive Multifocal Leukoencephalopathy ... caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability, has occurred in patients who have received TYSABRI

The John Cunningham (JC) virus is a common virus that is harmless in most people but can cause progressive multifocal leukoencephalopathy (PML) in people with weakened immune systems. 2 2

From the Research

Definition and Characteristics of JC Virus

• The JC virus, also known as JC polyomavirus (JCV), is a type of human polyomavirus that establishes an asymptomatic latent and/or persistent infection in most of the adult population 3.
• JCV is the established etiological agent of the debilitating and often fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML) 4.
• The virus is neurotropic, meaning it infects the central nervous system, and is typically found in immunocompromised individuals 5.

Infection and Disease Progression

• Most healthy individuals have been infected with JCV and generate an immune response to the virus, yet remain persistently infected at subclinical levels 4.
• The onset of PML is rare in the general population, but has become an increasing concern in immunocompromised patients, where reactivation of JCV leads to uncontrolled replication in the CNS 4.
• 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 5.

Immune Response and Treatment

• The humoral immune response, measured by the presence of virus-specific immunoglobulin G (IgG) in the blood or by intrathecal synthesis of IgG in the cerebrospinal fluid (CSF), is unable to contain the progression of PML 6.
• CD4+ T lymphocytes and CD8+ cytotoxic T lymphocytes play a crucial role in recognizing and responding to JCV infection, and may be important in preventing PML disease progression 6.
• Combination treatment of low-dose, long-term immunoglobulin and mirtazapine has been shown to be effective in treating PML caused by JC virus infection 7.