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RNA pol, replication fidelity

Andy Pekosz pekosz at shy.neuro.upenn.edu
Sat Dec 2 07:39:45 EST 1995

In article <199512011622.KAA17719 at borcim.wustl.edu>,
brett at BORCIM.WUSTL.EDU (brett) wrote:

> >Question for anyone.   
> >
> >Recently, I've attended a few seminars on viral pathogenesis.  An 
> >interesting topic that seemed to crop up from time to time was that a few 
> >RNA viruses (most notably Ebola and Dengue) show a high replication 
> >fidelity.   The question of course is why?  Why, should one virus 
> >show high rates of mutation and others not. 
> >Scott Hoffman
> >Graduate Student
> >schoffma at badlands.nodak.edu
> However, by growing the virus, you are
> imposing selection for the virus which grows best. Since we don't know all
> the interactions these viruses have with their host, its hard to speculate
> how well adapted a "wild type" strain is. However, bear in mind that the
> viruses you mention have compact
> genomes, and mutations are often likely to be deleterious, (although they
> are much larger than picornas, for example which can bear a large mutation
> load). A better way to measure mutation for these viruses would be
> reversion frequency of an engineered mutation, but no-one has done this
> yet, to my knowledge.
> Brett Lindenbach

There is an interesting paper in Journal of Virology 69(12):8132 on the
complete sequencing of a strain of Sin Nombre virus (the hantavirus that
causes respiratory distress syndrome out in the western US).  The authors
sequence the virus from an autopsy sample and isolate the virus from a
mouse found in the patient's home, then compare the two sequences.  The
result is only 16 nucleotide changes in a genome that is approximately
11,000 bases and none of the changes effect the amino acid coding
sequence.  The isolated virus was passaged at least 7 times in naive mice
or cell culture before sequencing.  The number of changes seems very low
to me, especially given the fact that the virus
saw 2 hosts and an artificial cell culture system before sequencing.  Maybe
this 'RNA polymerase fidelity' issue is not a generic RNA virus property, but
a property of specific RNA viruses?

Andrew Pekosz              
Depts. of Neurology and Microbiology
University of Pennsylvania Medical Center
255 Clinical Research Bldg.
415 Curie Blvd.
Philadelphia, PA 19104

phone:   (215) 898-3502
fax:  (215) 573-2029
email:   pekosz at shy.neuro.upenn.edu

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