QUALITATIVE ASSESSMENT OF RETROVIRAL
ACTIVITY IN HUMAN BRAIN AND TISSUES
Wolfgang Seifarth, Udo Zeilfelder,
Bigit Spiess, Rüdiger Hehlmann and Christine Leib-Mösch
III. Medizinische Klinik,
Universitätsklinikum Mannheim
We have developed a fast and reliable
high throughput method for the investigation of retroviral activity in
biological samples. The qualitative assay allows detection as well as
identification of most known retroviral reverse transcriptase (RT) – related
nucleic acids and combines multiplex polymerase chain reaction (PCR) using
fluorochrome (Cy3) – modified primer mixtures and glass DNA chip hybridization.
As part of our ongoing search for
disease-relevant human endogenous retroviruses (HERV) we have been investigating
the activity of HERV elements in human brain and other tissue samples.
Employing the microarray hybridization RNA samples derived from a panel of
various human tissues (n=17) were tested for RT-related transcripts
representative for almost all known HERV families of the human genome. Qualitative
evaluation of chip hybridization signals revealed distinct HERV activity in the
human tissues under investigation suggesting that HERV elements are active in
human cells in a tissue-specific manner. In human brain samples (cortex)
transcripts of HERV-K superfamily members, HERV-W, HERV-R, HERV-F, ERV9, and
HERV-E were observed. Differences in the HERV activity profiles observed
between the brain sample of an unaffected control person and an untreated
patient with acute-onset schizophrenia point to the possibility that some HERV
elements may be differentially regulated in neurological disorders. It is
not clear yet, whether the observed HERV activity variations reflect
inter-individual differences due to a different genetic background or are
specifically related with the disease. Further investigations focusing on
the analysis of tissue samples derived from different brain regions of patients
with schizophrenia, bipolar disorders as well as matched unaffected controls,
will grant more insight in the connection between HERVs and schizophrenia.
Poster: