Ok, so the CDC has confirmed..and other things!

[Ian A. York]

In article <Pine.SOL.3.91.950513223627.520C-100000-100000 at corona> Patrick O'Neil <patrick at corona> writes:
>
>I do not know how true or reliable this information is but I would find 
>it remarkable that particularly an RNA virus is so stable as to remain 
>virtually unchanged for nearly 20 years UNLESS the virion is very robust 
>and able to survive inertly in the environment for a long time (wow, hows 

	I agree that if indeed this is confirmed it is remarkable.  Again 
if true, I would still think that survival for 20 years in the 
environment is less likely than in a host species.  The fact that the 
previous Ebola epidemics burnt out and didn't keep re-exploding suggests 
that environmental survival is an unlikely explanation.

>A host within which it is so benign that the host's immune system ignores 
>it or makes no real effort?  Not bloody likely.

No, but it seems to be the least unlikely of a series of unlikely 
possibilities.  (Eliminate the impossible . . . )  It does suggest that 
the host/virus interaction for the 'real' host is very precise.  I'm not 
an RNA virologist, but it seems to me that LCMV is pretty stable in the 
tolerant mouse infection.  

Out of idle curiousity, I've been poking around the Ebola genome 
sequences in genbank and embl, and I ran across the reference 

Volchkov, V.E.; Blinov, V.M.; Netesov, S.V. 
FEBS Lett. (1992) 305:181-184
The envelope glycoprotein of Ebola virus contains an 
immunosuppressive-like domain similar to oncogenic retroviruses. 

The similarity is not spectacular, but it's there - running the gp 
through BLAST pulls out many of the oncogenic retroviruses, with 
homologies upward of 30% over reasonable stretches.  The 
immunosuppression associated with those viruses is in itself also not 
spectacular - i.e. the sequence is immunosuppressive, but we aren't 
talking about a total shutdown.  (This is going on memory, by the way.  I 
haven't reviewed those papers recently.)  

It seems possible to me that the natural host for Ebola establishes a 
persistent and possibly tolerant infection.  If tolerance, rather than 
constant immune evasion, is the situation, then it seems to me that there 
would be pressure on the virus *not* to mutate.  Mutants would be 
eliminated, right?  Arguing from LCMV, this may mean that the host is 
infected when the immune system is tolerizable - i.e. imature; this implies 
mammals, to me (maybe birds), although I suppose spread into the immature 
egg of a reptile is also possible.  This could be transplacental or 
neonatal; neonatal particularly in rodents, in which there is a longish 
window of immune immaturity post partum.  Building further on extremely 
shaky evidence, I lean toward a neonatal infection.  If the immune 
suppressive regions are real, the implication is that the virus is 
prepared to deal with at least a partially competent immune response.  
This scenario implies that the virus infects, suppresses the immune 
response temporarily and weakly until it establishes tolerance, then 
persists without causing spectacular disease.  

I'd be very interested in knowing more about the cell-mediated immune 
response in people infected with Ebola.  Is it appropriate?  Is there a 
bias toward CD4 or CD8 responses, which would imply a block on he other 
arm?  Is there evidence of tolerance?  Do survivors show a different 
response than those who succumb?  There is no evidence that a persistent 
infection is ever established in humans or other primates, but 
nevertheless this might be a useful appraoch to explaining the viral 
virulence.

Ian
-- 
Ian York   (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-3921     Fax  (617)-632-2627