HUMAN ENDOGENOUS RETROVIRUS W IN SCHIZOPHRENIA

Exposure

to various infections during early life has been associated with the development

of schizophrenia in early adulthood.  Also, the differential presence of

antibodies to infectious agents has been detected in patients with a diagnosis

of schizophrenia as compared to healthy controls.  Studies aiming at identifying

the differential presence of infectious agents in postmortem brain tissue

from individuals with schizophrenia as compared to healthy controls have,

The

underlying reason for our findings of HERV-W related RNA in the CSF, brain

tissue and plasma of individuals with schizophrenia is currently not known. 

Other investigators have suggested that the induction of transcriptional

activity of certain HERV families, including HERV-W may be related to

In order

to investigate if exogenous infections may influence the transcriptional

activity of HERV-W related genes we infected HFF cells with different titers of

the following agent; T. gondii, HSV-1, influenza A/WSN/33 or N.

caninum.  In these infected cells, the transcriptional activity of the

following genes were quantified by real-time PCR; HERV-W env, GCM1,

Infection

of the HFF cells with influenza A/WSN/33 resulted in pronounced transcriptional

activation of HERV-W env encoded transcripts.  The human ortholog of the

drosophila gene glial cell missing 1 (GCM1) has been reported to control

the transcriptional activity of syncytin in human syncytiotrophoblasts. GCM-1

was transcribed at relatively high levels in HFF cells infected with influenza

A/WSN/33 virus as compared to mock-infected cells.  No effect on the

transcriptional activity of the genes encoding the receptors for the HERV-W

envelope protein (hASCT1 & 2) was seen except for N. caninum that

strongly elevated the transcriptional activity of the gene encoding hASCT2 and

Neurons

in the upper brainstem have, in animal studies, been shown to be the target for

a number of infectious agents after both intracerebral and intranasal

inoculations.  In light of our findings in vitro we found it interesting

to quantify the transcriptional activity of the genes encoding HERV-W envelope

and ASCT2 in tissue from this brain region.  In the group of individuals that

had suffered from schizophrenia there was a significant positive correlation

(p=0.0053) between elevated transcription of the genes encoding HERV-W envelope

CONCLUSION: Infectious agents may influence the transcriptional activity of

certain HERV loci.  This may be mediated, in part, by transcriptional activation

of GMCM1.  The present findings in human postmortem samples indicate an aberrant

transcriptional activity of certain HERV-W loci apparently affecting the