viral pathogenesis

Chris Upton cup at
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  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

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
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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