Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome (IRIS)

Area of Science:

• Neurovirology
• Immunology
• Pathology

Background:

• Progressive multifocal leukoencephalopathy (PML) is a serious brain infection caused by the John Cunningham (JC) virus.
• JC virus, a polyomavirus, typically remains latent in healthy individuals but can reactivate in those with compromised immune systems, such as patients with HIV or undergoing immunosuppressive therapy.
• PML emerged as a critical opportunistic infection of the central nervous system (CNS) during the HIV/AIDS epidemic and has seen a resurgence due to modern immunosuppressive treatments.

Purpose of the Study:

• To review the virological aspects of JC virus infection in the CNS.
• To detail the pathology of PML and PML-IRIS, focusing on the immune system's role.
• To elucidate the mechanisms driving inflammation in PML and PML-IRIS.

Main Methods:

• Review of existing literature on JC virus, PML, and PML-IRIS.
• Analysis of the immunological mechanisms underlying PML pathogenesis.
• Examination of the role of cytotoxic T cell responses in PML and PML-IRIS.

Main Results:

• PML and PML-IRIS are primarily caused by JC virus infection of oligodendrocytes and, to some extent, neurons in the CNS.
• An intact cellular immune response is crucial for preventing PML.
• Immune reconstitution, while potentially clearing the virus, can trigger severe inflammatory responses (PML-IRIS) due to massive destruction of infected cells.

Conclusions:

• PML pathogenesis involves JC virus infecting glial cells and neurons, with inflammation driven by T cell responses.
• PML-IRIS represents a dangerous exacerbation of PML due to a hyperactive immune response during immune reconstitution.
• Understanding the immune system's role is critical for managing PML and preventing severe outcomes like PML-IRIS.