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2015 ; 230
(12
): 2869-74
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Animal Models for Progressive Multifocal Leukoencephalopathy
#MMPMID26041694
White MK
; Gordon J
; Berger JR
; Khalili K
J Cell Physiol
2015[Dec]; 230
(12
): 2869-74
PMID26041694
show ga
Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating
disease of the CNS caused by the human polyomavirus JC (JCV). JCV replication
occurs only in human cells and investigation of PML has been severely hampered by
the lack of an animal model. The common feature of PML is impairment of the
immune system. The key to understanding PML is working out the complex mechanisms
that underlie viral entry and replication within the CNS and the
immunosurveillance that suppresses the virus or allows it to reactivate. Early
models involved the simple inoculation of JCV into animals such as monkeys,
hamsters, and mice. More recently, mouse models transgenic for the gene encoding
the JCV early protein, T-antigen, a protein thought to be involved in the
disruption of myelin seen in PML, have been employed. These animal models
resulted in tumorigenesis rather than demyelination. Another approach is to use
animal polyomaviruses that are closely related to JCV but able to replicate in
the animal such as mouse polyomavirus and SV40. More recently, novel models have
been developed that involve the engraftment of human cells into the animal. Here,
we review progress that has been made to establish an animal model for PML, the
advances and limitations of different models and weigh future prospects.
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