RETROVIRUS W IN SCHIZOPHRENIA
Lorraine Brando, Krister Kristensson, Robert H. Yolken and Håkan
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,
however, been negative.
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
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,
SLC1A4 and 5 (encoding hASCT1 & 2).
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
to some extent hASCT1.
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
and ASCT2. In the control group no such correlation was seen.
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
transcriptional activity of the gene encoding the ASCT2 amino acid transporter.