Epigenetic Search for Retroviruses in Major Psychosis
A Petronis, P-X Kan, Yolken RH, and the Stanley
Neuropathology Consortium
Recent studies of CSF and frontal cortex from schizophrenia
patients have detected retroviral RNA with 90-95% homology to the multiple
sclerosis retrovirus (MSRV). In a similar way, CSF and frontal cortex from
patients affected with bipolar disease revealed RNA homologous to retroviruses
erv K-10, while control subjects exhibited a higher proportion of pHE.1 and erv
min. It is not clear, however, which one(s) of hundreds of endogenous
retroviral sequences (ERVs) exhibit transcriptional activity in individuals
affected with major psychosis and controls. Epigenetic strategies may help
to differentiate between the ‘active’ retroviral sequences. Experimental
findings from other laboratories have demonstrated that DNA methylation plays a
role in inhibiting transcription of retroviral genomes. Our hypothesis is
that transcriptionally active ERVs, which have been detected in affected
individuals, are demethylated while inactive ERVs are hypermethylated.
We are performing a comprehensive analysis of DNA methylation
status at and around retroviral sequences exhibiting DNA homology with the ERVs,
which are differentially expressed in affected individuals in comparison to
controls. Brain specific DNA samples are being investigated using
methylation sensitive restriction enzymes and Southern blot-hybridization
technology. The blots are subjected to subsequent hybridizations with DNA
probes which are homologous to the following ERVs: MSRV, ervK-10, pHE.1 and erv
min. Our plan is to screen 15 post-mortem brains in each group of
individuals who were affected with schizophrenia, bipolar disease, and
controls. The hypomethylated ERV sequences will be subjected to cloning,
sequencing, and further investigated for neurotoxic effects.