Epigenetic Search for Retroviruses in Major Psychosis

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.