Comments on: Viral quasispecies and bottlenecks

By: reverse phone lookup

reverse phone lookup — Thu, 17 Nov 2011 21:23:00 +0000

Looks like you’ve done your research very well.

By: List Pay Day Pro 2

List Pay Day Pro 2 — Tue, 15 Mar 2011 02:19:00 +0000

Wow this stuff is intense!

By: Joe

Joe — Wed, 25 Aug 2010 01:32:39 +0000

This is a tricky subject that actually needs more depth to properly explain than is provided here. This explanation and the diagrams mislead the reader into assuming the polymerase “knows” to fix those base pair positions that allowed the virus to escape whatever the bottleneck was. This is a dangerous mindset to get into because it doesn't accurately reflect what is happening. It is just as likely for viral RNA's after the bottleneck event to have mutations at those particular postitions that cause it to revert to a pre-bottleneck sequence. The polymerase is always making random mutations, the environment is the deciding factor on how those mutations effect the fitness of that viral quasispecies.

By: Influenza variations | Mystery Rays from Outer Space

Influenza variations | Mystery Rays from Outer Space — Tue, 27 Apr 2010 11:27:29 +0000

[...] sequence even though the vast majority of the genomes are different from that average. (Here and here are Vincent Racaniello’s explanations at The Virology Blog.) Two sequences is just two [...]

By: Viral quasispecies and bottlenecks virology

Viral quasispecies and bottlenecks virology — Sat, 12 Sep 2009 05:47:36 +0000

[...] Read more: Viral quasispecies and bottlenecks [...]

By: profvrr

profvrr — Tue, 21 Jul 2009 00:45:45 +0000

Sorry, your comment was held in the spam queue for some time…the
answer is, with current sequencing techniques, we only see the 'master
sequence' and do not get any hint of the diversity. Deep-sequencing
methods might allow us to see exactly what is coming out of one host
versus another; but the limitation will be the error rate of the
polymerase used to amplify the RNA for sequencing.

By: profvrr

profvrr — Mon, 20 Jul 2009 17:45:45 +0000

By: gsgs

gsgs — Thu, 09 Jul 2009 10:44:31 +0000

but why then don't we see some differences, sometimes ?
The mutations should add over time, still we only see ~32 mutations
per year, less than one in average per host in flu-A, half of that in flu-B

When we find exactly the same sequences several times in Mexico and elsewhere,
is there still reason to believe the viruses are different ?
Is the virus uniquely determined by the sequence (assuming one infectious virus only)
The envelope is stolen from the cell, maybe Mexican,Argentine pople have different
cell-membranes

By: Viral quasispecies and bottlenecks | Shed Kits

Viral quasispecies and bottlenecks | Shed Kits — Wed, 27 May 2009 02:06:40 +0000

[...] Viral quasispecies and bottlenecks Posted by root 18 hours ago (http://www.virology.ws) One of these genomes indicated by the arrow is able to survive a your comment is awaiting approval by a moderator you are correct a human infected with h1n1 or any virus would shed blog comments powered by disqus wordpress admin content on this site is li Discuss | Bury | News | viral quasispecies and bottlenecks [...]

By: phogdog

phogdog — Sun, 24 May 2009 22:35:24 +0000

Thank you. This is very helpful.

Your answer I think also took care of my next question… When infected people are tested or swabbed for virus particles, a mixture of particles are being sequenced simultaneously, by whatever magic blackbox/sequencing machine/process you use, the amino acid sequences from the sample are decided by a 85% (?) level of agreement on an single position. And if a position has above 15% (?) difference at a single position, that this would generally constitute a single mutation point on that strand of the RNA by definition.

Could a single nasal swab test then ever provide a situation where a single position had a 50%-50% variability, thus providing two different isolate sequences? Or is this just not mathematically going to happen due to low rate of mutation against the length of RNA?

By: profvrr

profvrr — Thu, 21 May 2009 23:12:34 +0000

You are correct - a human infected with H1N1 (or any virus) would shed
a population of diverse particles. The sequence that is reported is a
consensus, similar to that which we defined here at virology blog in
previous posts. It does not at all reflect the various mutations
because each one is not sufficiently predominant to be detected in the
sequence analysis. In the old days of sequencing, we used to say that
a mutation had to be in at least 15% of the population to be detected
by sequencing. I'm not sure what the detection limit of the new
methods is. But this brings up an interesting problem, crystallized by
Luis Villareal, who wrote to me: "In my judgement, of all the fields
of human virology, the flu field has curiously been the least affected
by the developments of quasispecies theory (for example, almost no
papers have attempted to measure flu quasispecies composition via
pryosequencing etc.). Flu researchers believe in the master template
as being the fittest type. I think this has been to their detriment
and is currently confusing the field as we witness the evolution of
emergence. I would be willing to bet money, that if the quasispecies
composition were measured, we would see clear differences between
those patients that died in Mexico compared to the much less virulent
outcome in the USA."

So basically the sequences we see may not reflect the mutations that
are important for virulence and transmission. You have hit the nail
right on the head with your question.

By: profvrr

profvrr — Thu, 21 May 2009 22:38:40 +0000

By: phogdog

phogdog — Thu, 21 May 2009 16:27:36 +0000

I am still trying to wrap my brain around the implications of quasispecies theory and the high rate of RNA mutations.

Would this mean that a human infected with the novel H1N1 would be expelling new virus particles with a range of RNA sequences?

So when we see the genetic sequences for a particular isolet in the CDC files, the same individual is probably producing other particles with other genetic sequences at the same time?

Or am I missing something elemental here?

By: profvrr

profvrr — Thu, 14 May 2009 00:00:33 +0000

I'm writing a post about this work now, but if you want a head start:
doi:10.1371/journal.ppat.0010011.

By: The number of possible viral variants

The number of possible viral variants — Wed, 13 May 2009 18:13:39 +0000

[...] you have been following our discussion of quasispecies here on virology blog, you might be wondering exactly how many possible variants there are for a [...]

By: thor183

thor183 — Wed, 13 May 2009 16:52:27 +0000

"Recently it became experimentally feasible to test the idea that viral populations, not individual mutants, are the target of selection. We’ll examine those data next."

Is there someplace to read about this experiment? I'll even try to muddle my way through a peer-reviewed research paper.

Being a software guy, I'm finding the algorithmics of these natural processes fascinating.