Prevention and therapy of JC polyomavirus-mediated progressive multifocal leukoencephalopathy – a realistic possibility?

Abstract

Progressive multifocal leukoencephalopathy (PML) is a serious opportunistic infection of the brain caused by the JC polyomavirus (JCPyV). PML occurs when immune control of persistent infection with JCPyV fails, the virus mutates and changes its cellular tropism, enters the brain and infects astrocytes, oligodendrocytes and, in particular cases, also neurones. Currently, there is no therapy for this often fatal disease. A number of approaches have failed, and only the restoration of protective immunity, if possible, can lead to clearance of the virus once PML has occurred. During the last two decades, investigators have attempted to understand the factors contributing to the development of PML, which immune mechanisms are involved in immune surveillance, and which in clearing JCPyV from the brain once PML has occurred. Recent data suggest that both CD4+ and CD8+ T cells of the cellular immune system, and also JCPyV-specific antibodies, are involved in protection against PML and in resolving the opportunistic infection. Based on the current immunological data, prophylactic and therapeutic vaccination strategies have been proposed, and first treatment attempts in PML patients have provided promising results that indicate therapeutic vaccination may be feasible.

Progressive Multifocal Leukoencephalopathy

“…Additional promising biomarkers for PML prediction may include neurofilament light chain levels in blood, host genetic tests, monitoring of JCV genetic variants in various tissues, and prophylactic vaccine development e.g., based on JCV VP1 virus-like particles in populations at risk. 34,55,56 These strategies were mainly proposed for and studied in MS populations and did not exceed the experimental level. Considering PML being a rare disease, further validation and clinical implementation particularly outside the MS field may prove to be challenging.…”

Long-term outcome of natalizumab-associated progressive multifocal leukoencephalopathy in Austria: a nationwide retrospective study

“…NAT blocks the alpha4-beta1 integrin receptor on lymphocytes and thereby prevents migration of immune cells into the brain [ 1 , 2 ]. Its use carries a uniquely high risk for the development of progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by human polyomavirus 2 , also known as JC polyomavirus (JCV) [ 3 , 4 ]. NAT-associated PML (NAT-PML) is a potentially fatal condition that causes substantial morbidity among survivors [ 5 , 6 ].…”