viral pathogenesis

Michael G. Kurilla mgk2r at Virginia.EDU
Mon Aug 2 09:25:49 EST 1993


cup at bones.biochem.ualberta.ca  writes:
> In article <1993Jul30.141357.12888 at Virginia.EDU>, mgk2r at Virginia.EDU
> ("Michael G. Kurilla") wrote:
> > 
> > I have recently have gotten hooked into these forums and I am
> > impressed with the range of topics.  The virology group is a
> > particular interest since I work on EBV (Epstein-Barr virus).
> > I am most interested in aspects of viral pathogenesis.  While
> > this touches (alot) on immunology, the mainstream immunologists
> > seem to ignore anything that happens from the viral end beyond
> > the generation of peptide epitopes.  Therefore this group seems
> > most appropriate.  Since viruses appear to have figured out the
> > most feasible ways of doing things, lessons from other viral
> > systems would probably be instructive to all.  Is there
> > interest out there for people thinking out loud about these
> > issues?
> 
> 
> Sure is! I'm interested in poxviruses..... another bunch of big guys. These
> viruses have a variety of methods for countering the immune system. Most
> recently I've been looking at proteins secreted from infected cells. These
> include virally encoded proteins that block, TNF and IFN-gamma of the host.

We have been using vaccinia virus recombinatnts for a large
part of our work in defining EBV T cell epitopes.  Is the
mechanism of the IFN-gamma block known?  Kevin Moore at DNAX
has told me that in assays of IL-10 activity, the vaccinia
control supernatants have considerable IFN-gamma secretion
inhibition when he was trying to measure vaccinia derived
mIL-10 that we had made.

I'm interested in this because we would like to use vaccinia
recombinants expressing individual EBV genes for memory CTL
reactivation in vitro.  In the EBV system, lytic or productive
genes are difficult to study immunologically since pure
replicating cultures of EBV do not occur; most of the culture
remains latent.  The latent genes stimulate a large memory CTL
activity which swamps out the specific lytic memory CTL.

Some labs have reported using vaccinia recombinants as
stimulators, but there is more talk than published literature.
Would it be possible to add antiserum specific for the putative
soluble vaccinia derived product?  Would that increase the
degree of CTL reactivation?  It is known that vaccinia specific
CTLs are hard to find in people.  Every one invokes route of
inoculation and limitations in only sampling the PBL
compartment as possible reasons, but vaccinia derived factors
could also be to blame.

Any info.

Thank
Mike Kurilla
University of Virginia
mgk2r at pcmail.virginia.edu



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