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The genetic stability of Ebola virus

Steven Enkemann enkemans at dc37a.nci.nih.gov
Fri Aug 4 13:03:30 EST 1995

In article <evans-2807951508000001 at ganymede.ahabs.wisc.edu>,
evans at ahabs.wisc.edu (PSE) wrote:
> Does it surprise anybody that an RNA virus that has been replicating in
> the wild for almost 20 years has accumulated very few variations at the
> nucleic acid level?  Sanchez et al do not comment about the resulting
> proteins, so many or all of these mutations may have been silent.  
   It doesn't suprise me at all.  High rates of mutation can easily be
offset by strong selective pressure.  Ebola like most other RNA viruses
has a tremendous capacity to evolve.  But unless new types of selection
are imposed upon the virus it is very likely to remain nearly identical
for a long time. 

More below.

> Is this the kind of variation that would be expected from an RNA virus
> over such a time period due to genetic drift (ie: neutral evolution")?  
> Is there any data about genetic drift in filoviruses, or other RNA
> viruses?
   The answer to these questions appears to be yes.  Stuart Nichols has
done a great deal of work on the evolution of Vesicular Stomatitis Virus
(VSV).  Isolates of the New Jersey serotype of this virus have been around
for more than 50 years and yet there is little genetic change.  For
references to this work see:

Nichol, S.T. (1987) Molecular epizootiology and evolution of Vesicular
stomatitis virus New Jersey. J. Virology 61: 1029-1036.

Nichol, S.T., Rowe, J.E., and Fitch, W.M. (1989) Glycoprotein evolution of
Vesicular stomatitis virus New Jersey. Virology 168: 281-291.

Bilsel, P.A., Rowe, J.E., Fitch, W.M., and Nichol, S.T. (1990)
Phosphoprotein and nucleocapsid protein evolution of Vesicular stomatitis
virus New Jersey. J. Virology 64: 2498-2504.

Even though the VSV RNA-dependent RNA polymerase is quite error prone
(Drake, J. W. (1993) Rates of spontaneous mutation among RNA viruses. PNAS
90: 4171-4175. and Holland, J., Spindler, K., Horodyski, F., Grabau, E.,
Nichols, and VandePol, S. (1982) Rapid evolution of RNA genomes. Science
215: 1577-1585.) the overall genome accumulates mutations quite slowly. 
Even in a laboratory situation this is true.  We have compared the genome
of a virus passaged several hundred times in the laboratory to a frozen
stock from which it was derived and found very few differences among over
8 kilobases of genome (unpublished observations).  This suggests once
again that if the selective pressure remains constant the resultant genome
will remain constant.  

> Does the lack of genetic changes imply anything about Ebola's natural
> reservior?   

   To me it suggests that the natural reservoir is stable.  If this is
true it further suggests that the reservoir is not adversly affected by
the Ebola virus and therefore has no reason to try to eliminate it.

   One further comment on the suggestion by some about silent mutations. 
In the VSV studies mentioned above the vast majority of the changes were
'silent mutations'.  However this term applies to nucleotide changes in
relation to protein coding effects.  For all of the negative strand RNA
viruses the genome serves more than just as a source of information,
coding for the viral proteins.  The genome is a vital part of the
structure of the virus.  The template for transcription is not RNA.  It is
a ribonucleoprotein complex.  How the nucleoprotein interacts with the
genome is influenced by the nucleotide sequence.  Mutations that appear to
be silent based on coding capacity may very well greatly influence the
structure of the virus.

Steven A. Enkemann PhD.

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