>> >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
>> 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?
>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
Again, I have to state that retrospective analysis on field isolates
biases the study towards LIVE VIRUSES. Thus, the range of sequence space
you'll examine does correlate with replication fidelity, but also has to
do with a very complex virus:host relationship. Therefore, it would be
foolish to surmise that the replicase didn't produce mutants just because
you didn't see them. I'd argue that they were just selected against.
I see two concepts that are getting intertwined presumptously:
replication fidelity, and selection. The ideal way to study the former is
in the absence of the latter. Studying purified RNAP would be one approach.
Another would be to study the frequency of reversion of a silent mutation.
BTW, the yelllow fever (a cousin of dengues) vaccine strain 17D contains only
0.6% nucleotide differences from its virulent parent, Asibi. It was derived
by >240 serial passages.
Program in Immunology
Washington University - St Louis
brett at borcim.wustl.edu
"I own my own pet virus. I get to pet and name her." - Cobain