I've
been working on the talk and since the class does not have a strong
background
on immunology, I did a search which would help them understand my
talk
better.Here are the sites that I
have found:
Introduction
to Immunology:
http://sprojects.mmi.mcgill.ca/dir/immunology.asp
Understanding
Autoimmune Disease:
http://www.niaid.nih.gov/publications/autoimmune/autoimmune.htm
Systemic
Lupus Erythematosus:
http://www-medlib.med.utah.edu/WebPath/TUTORIAL/SLE/SLE.html
Epstein-Barr
Virus:
http://www.ufla.org/~jvankomen/ebv.htm
Please
make it a required reading.If they
don't read it they will not know
what
I am talking about.
Abstract
Antibodies
to double stranded DNA (dsDNA) are the hallmark of the chronic autoimmune
disease Systemic Lupus Erythematosus (SLE).The
etiology of this disease is unknown.However,
previous studies have suggested that viruses may play a role.One
such virus that has been implicated in the onset of SLE is the Epstein-Barr
virus (EBV).Studies by James et
al. (1995) have demonstrated that rabbits immunized with a peptide homologous
to Epstein-Barr nuclear antigen-1 (EBNA-1), a major DNA binding protein
encoded by EBV genome and the spliceosomal ribonucleoprotein Sm (SmRNP),
developed antibodies to EBNA-1, SmRNP, and dsDNA.It
is not clear why antibodies to dsDNA arose.We
hypothesize that the complexing of EBNA-1 to eukaryotic dsDNA may render
the DNA immunogenic and lead to an anti-dsDNA antibody response.To
test this hypothesis we immunized BALB/c mice intramuscularly with an EBNA-1
expressing plasmid (pDY-6a).Control
mice were injected with a plasmid lacking any EBV sequence (pUC18).pDY-6a
is known to replicate autonomously in murine cell lines.Prior
to injection, we demonstrated that pDY-6a
could replicate in a murine cell line for at least 15 days.Using
the polymerase chain reaction (PCR) we were able to demonstrate the maintenance
ofpDY-6a
in mouse tissue for 15 days post injection.The
expression of the viral antigen in mouse tissue was also demonstrated by
reverse transcriptase polymerase chain reaction (RT-PCR).After
boosting at two week intervals, immunize mice were found to produce IgG
antibodies to EBNA-1 as well as antibodies to dsDNA.The
IgG antibodies to dsDNA appeared three weeks following the appearance of
antibodies to EBNA-1.This is the
first time that in vivo expression of EBNA-1 in the mouse has been
shown to elicit an anti-dsDNA response and suggests that EBV may play a
role in the etiology of SLE.
Supported
by NIH R21A147581