Saturday, August 15, 2009

PML A Stochastic event before brain infection

per Dr Joe Berger's talk at AAN. A number of necessary events must occur
1. 80 % of individuals are infected with JC virus, virtually all by age 20.
2. Latent primary viral infection must occur, involving spleen, kidney, bone marrow, tonsil, oropharyngeal lymph nodes and other tissues. Controversial whether it is latent in brain. Virus appears incapable of replicating in brain. Must have receptor to allow virus to bind.
3. Infected cell must have NF 1X to allow virus to replicate
4. 98 base pair tandem repeat within nucleus probably within B cells must allow insertion to allow replication of virus within brain (b cells must activate)
5. Failure of immunosuppression in periphery and allow detectable JC virus in blood (see IgG antibody in blood suggesting its reactivated infection)
6. Periodic reexpression of JC virus in PBMC
7. Entry of JC virus into brain and allowance of productive oligodendrocyte function
8. Failure of immunoregulatory function in the brain

Natalizumab-- may cause release of B cells and ciruculate, premature and mature B cells and increased transcription factors resulting in a productive infection. Decreased immunosurveillance in brain. JC toxic circulating t lymphocytes are important. Also loss dendritic cells responsible for antigen presentation.

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