RNA pol, replication fidelity

bhjelle at unm.edu bhjelle at unm.edu
Wed Dec 6 09:46:16 EST 1995


In article <199512030002.SAA24798 at borcim.wustl.edu>,
brett <brett at BORCIM.WUSTL.EDU> wrote:
>>

(on low sequence variation generated by passage of RNA viruses
in nature and in cell culture)
>
>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

Well said. This is a recurrent misunderstanding. While
there are experimental systems suitable for studying replication
fidelity of RNA-dependent RNA polymerases (RDRP), comparison
of host-associated virus sequences in nature and tissue culture-
passaged virus sequences is not one of them. In addition to
profound selective pressures on the virus, there is also
the problem that viruses exist as *quasispecies* in nature.
That is, there are many sequence variants present in the
host and in the tissue culture-grown virus population. When
you sequence the virus, you are generally looking at predominant
quasispecies (ie, those present at highest abundance). This
is not to imply that sequence comparisons between host-
associated viruses and passaged viruses are not useful, just
that they will not help you much to understand RDRP fidelity.

Brian







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