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viral pathogenesis

Chris Upton cup at bones.biochem.ualberta.ca
Mon Aug 2 18:40:13 EST 1993

In article <1993Aug2.142549.18611 at Virginia.EDU>, mgk2r at Virginia.EDU
("Michael G. Kurilla") wrote:
> cup at bones.biochem.ualberta.ca  writes:
> Stuff deleted> > 
> > 
> > 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

The inhibiting protein is a secreted homolog of the IFN-gamma receptor.
I first found this in myxoma virus, the protein is secreted in HUGE
(Science 258:1369-1372 1992). There is an equivalent gene in other
poxviruses, but they don't produce as much of this protein. The myxoma
protein can be X-linked to INF-gamma and is pretty specific for rabbit
IFN-gamma, also the
protein blocks the protective effect of IFN-gamma in an VSV plaque assay.

It seems that while most poxviruses secrete a number of proteins which
active as virulence factors, only 1 or 2 are secreted at very high levels
and these are different in different poxviruses. Vaccinia also secretes an
IL-1 binding protein but does not have the functional TNF blocking protein
found in other poxviruses. 

Chris Upton
University of Alberta

As of Sept 1st 1993,  cupton at sol.uvic.ca
Department of Biochemistry & Microbiology
University of Victoria         
PO BOX 3055, Victoria          
BC V8W 3P6                     
(604)721-6507 phone        
(604)721-8855 fax

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