THE HUMAN ENDOGENOUS
RETROVIRUS W GAG PROTEIN
Sarven Sabunciyan1, Inna Ruslanova1, Serge Weis2,
Ida Llenos2, and Robert Yolken1
1Department
of Pediatrics, Stanley Division of Developmental Neurovirology, Johns Hopkins
University, Baltimore. MD; 2Neuropathology Laboratory, Stanley
Medical Research Institute, Bethesda, MD
Previously our laboratory
reported Human Endogenous Retro Virus-W (HERV-W) transcripts to be present in
CSF samples obtained from schizophrenia patients and HERV-W transcripts to be
overexpressed in schizophrenic brain tissue. In order to further examine the
possible involvement of HERV-W in schizophrenia, we developed an assay that
allows us to detect the presence of antibodies against the HERV-W gag protein.
The longest open reading frame for the HERV-W gag gene in the human genome,
which is present on chromosome 3, was cloned into a baculovirus DNA construct.
The HERV-W gag protein was then expressed in insect cells and purified using the
attached histidine tag. This purified protein was used as the antigen in the
ELISA assays
Sera from a case control
study containing untreated first episode schizophrenia patients and matched
controls were screened for the presence of antibodies against the HERV-W gag
protein. Sixteen out of the two hundred twenty screened samples resulted in
positive signals in the ELISA assays. All sixteen positive sera are from
individuals with recent onset schizophrenia. Currently we are verifying these
results by western blot analysis and we are also screening more serum samples in
order to determine the extent of the correlation between schizophrenia and
HERV-W. In addition to linking HERV-W sera Positivity with schizophrenia, these
findings raise some interesting questions regarding the expression of endogenous
retrovirus proteins in the human body. Why doesn’t everyone have antibodies
against the HERV-W gag protein? Are proteins from endogenous retroviruses
regarded as self by the immune system or are they expressed only in a small
subset of the population? Further work in our laboratory will also attempt to
address these questions.