POSTER

POSTER

 

 

COMPREHENSIVE

ANALYSIS OF HUMAN ENDOGENOUS RETROVIRUS (HERV) TRANSCRIPTIONAL ACTIVITY IN

HUMAN  TISSUES WITH A RETROVIRUS-SPECIFIC MICROARRAY

Oliver Frank,

Michelle Giehl, Chun Zheng, Ruediger Hehlmann, Christine Leib-Moesch and

Wolfgang Seifarth

Medizinische

Klinik III, Universitaetsklinikum Mannheim der Ruprecht-Karls-Universitaet

Heidelberg, Wiesbadener Str.7-11, D68305 Mannheim, Germany

 

 

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-related nucleic

acids and combines multiplex polymerase chain reaction (PCR) using fluorochrome

(Cy3)-modified primer mixtures and glass DNA chip hybridization.

 

Employing the microarray

hybridization assay RNA samples derived from peripheral blood (n=6) and from

mammary gland specimen (n=6) were tested for  RT-related transcript s(N=55)

representative for prominent HERV taxa of the human genome.  Qualitative

evaluation of chip hybridization signals revealed distinct HERV activity

suggesting that HERVs are active in human cells in a tissue-specific manner.

 

Furthermore, 105 post

mortem brain tissue specimen of the Stanley array collection (3 groups with 35

specimens each derived from normals and individuals with schizophrenia and

bipolar disorders, respectively) have been tested.  Evaluation of HERV

transcriptional activity profiles revealed that retroviral elements of class I

and II are active in prefrontal cortex in a tissue specific manner.  Transcripts

of HERV-K-superfamily subgroups HML-2, HML-4, HML-6, HML-9, HML-10 as well as

class I retroviral transcripts of HERV-W, HERV-F, ERV9, and HERV-E taxa were

observed in all specimen.  Comparison of HERV profiles obtained from SCZ,

bipolars and normal brain specimen revealed minor differences that could not be

linked to the disease status but seem to be characteristic for the genetic and

environmental background of the donor individual.

 

Interestingly, a MLV-related

sequence has been detected in 26% of all tested samples pointing to an

animal-born retrovirus associated with human brain. Further experiments are in

progress to elucidate origin and the putative role of this sequence for

neurological disorders.