Many roads lead to Rome, and tetherin down-regulation

While we are on the topic of IDiot Michael Behe, I thought now would be a good time to check in on our dear friend, HIV-1 Vpu!

What neat evolutionary tales do you have for us this week, HIV-1 Vpu?

Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a {beta}TrCP-dependent mechanism.

We discovered a while back that we have a whole 'new' component to our innate immune system we didnt know existed until we started to investigate the peculiar mutation rates within HIV-1 Vpu. This protein is called 'tetherin', and every cell in your body (not just your immune cells) make it in response to some viral infections. The result of this, is that progeny virions are 'tethered' to the surface of infected cells. Theyre trapped. Cant float off and infect someone else.

Well, HIV-1 Vpu has been mutating wildly in humans. Like, HIV-1 Env mutates a lot, but its under pressure from their hosts antibodies. Vpu mutated more than Env. Whats going on? Turns out Vpu was mutating in response to human tetherin, as one of Vpus 'jobs' is to degrade tetherin, thus freeing the babby viruses.

HIV-1 Vpu apparently degrades tetherin by tossing it into a lysosome (as opposed to how it degrades CD4, via proteasome).

However, HIV-2 also downregulates tetherin in infected cells, even though HIV-2 does not have a Vpu protein. This makes sense, as HIV-2 has to 'deal' with tetherin as much as HIV-1. Creationists have latched onto this fact as 'evidence' Vpu 'isnt really new or all that special in the first place', or as Behe calls it 'insignificant'. "Bawwwww, bot dem der HIVs do deh same things! Aint be nuttin ebolbing!"

Yes, HIV-2 also has a mechanism for downregulating tetherin. Its HIV-2s envelope protein that does it, since it has no Vpu. What happens, is, in HIV-2 infected cells, tetherin is downregulated at the cell membrane, but it is still upregulated in the cell as a whole as the cells normal response to viral infection. With HIV-1 and Vpu, tetherin is globally downregulated.

Evolution created two entirely different mechanisms, two entirely different solutions, to the exact same problem.

To quote Dembski/Marks totally super peer reviewed paper:

"The key contention of ID is that design in nature, and in biology in particular, is detectable. Evolutionary informatics, by looking at the probability requirements* of evolutionary processes, points to probability* sources beyond evolution and thus, indirectly, to a designer."

When Dembski and Behe bawww about the 'probability of X evolving', or the 'probability of Y evolving', there is no reason why X or Y needs to evolve, even if it already did. A might have been a perfectly 'right' answer. And B. And C. And D... Hell, E might have been the 'best' answer to the problem, but HIV-1 stumbled into X first, so there it is.

We know HIV-1 and 2 have figured out two independent solutions to the same problem, tetherin. Apparently, lots of other viruses have too (other retroviruses, ebola, etc). So how can you look at Feature X and proclaim 'Feature X is so exquisiteee! Its so very impossible to eeevolve! This amino acid change, that, eet does nut work! Design! Design!', when Feature X never had to evolve the way it did in the first place, and you have no friggen idea how many roads lead to Rome? This is another example of what I was getting at in this post.

Its random, and not random, and its very pretty. Quasispecies, chaos, order, its peaceful. I dont know why Creationists are so disturbed by it.

* Dembski calls probability 'active information' and 'informational requirements' for some reason. I have been advised 'not to play his rhetorical games' and to call those terms probabilities, so there ya go.

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So, does this point to the possibility of using a tetherin substitute (kinda like the way insulin is used) or something to enhance production of same, to fight this thing?

The condescending texan idiot said (in the charles jackson: expert thread, but my mobile refused to post my comment);
Jackson had a wider variety of wrong arguments and ERV stuck to correct arguments in her area of expertise. Therefore jackson won, therefore goddidit!
The condescending texan idiot.

*tumbleweed*

Dembski's "information" is really just probability measured on a logarithmic scale. It's all a rhetorical trick to say that "information" is "hidden" or "smuggled" when, if anything, the mathematical truth is exactly the opposite. (High Kolmogorov information in the fitness function means that the fitness landscape is incompressible and satisfies the Martin-Loef definition of randomness; a random, uncorrelated fitness function satisfies the Pure Noise condition, meaning that search algorithms will perform poorly.) If he called it "surprisal", as an information theorist should, nobody would be impressed.

Dembski could measure probability in equivalent M&Ms — "It's as improbable as finding one green M&M amid 10^150 red ones!" — but that doesn't mean a search algorithm actually contains candy.

Great post ERV!
I have a question brought on by this statement you made above:
"HIV-1 Vpu apparently degrades tetherin by tossing it into a lysosome (as opposed to how it degrades CD4, via proteasome)."
I have read many "issues" HIV/AIDS denialists state as to why they do not believe HIV causes AIDS. I have seen many studies that refute every one of these silly "issues" except when they say that science has not proven how HIV destroys CD4 cells.
Are proteosomes the culprit? Can you expond on this question of how HIV destroys CD4 cells?
I would very much appreciate it.
Thanks,
JTD

By J Todd DeShong (not verified) on 03 Sep 2009 #permalink

Totally off-topic (I promise to read later), but I wanted to pimp out the silly art of an acquaintance of mine. It's quite virally cute.

"Dembski's "information" is really just probability measured on a logarithmic scale. It's all a rhetorical trick to say that "information" is "hidden" or "smuggled" when, if anything, the mathematical truth is exactly the opposite."

What Dembski says is trivially true, that evolutionary algorithms aren't guaranteed to perform well on all fitness landscapes. Such is obviously true even if you don't invoke the NFL theorems, since the class of all fitness landscapes includes members with with discontinuities, non-differentiable neighborhoods, etc. It even includes non-computable landscapes, such as Kolmogorov complexity as an integer function, of the halting set. The problem is that evolution doesn't have to work well on all landscapes.

Todd, the explanation, as I understand it, (remember - I am just an engineer) is somewhat involved, so bear with me, and don't be offended that I'm using our hosts style.

First, some clarification. CD4 is a receptor on certain cells that HIV can bind to to gain entry. Those cells that express CD4 are called CD4 cells. This is an important distinction. When vpu tells the proteasome to nom CD4, this does not necessarily mean that it destroys the CD4 cells. This function of vpu is more like a squatter boarding up broken windows in a building so no other squatters can get in (and it also makes sure that all the babby viruses dont come back to the infected cell). Make sense so far?

That said, is does appear to have a role in the release of babby viruses beyond changing the locks after they go off to college. So it may play a role in the destruction of the CD4 cell. Im not exactly sure on the mechanisms involved here, this is just a 10 minute Google University degree.

So now, how does HIV kil CD4 cells? It seems to do it in two ways. When you first get infected, theres all these juicy CD4 cells for HIV to nom. It infects one, makes lots of babby viruses, and then the CD4 cell gets gutted like a salmon for caviar and all the babby viruses go spilling out to try and nom other juicy CD4 cells.

But as more CD4 cells get nommed, there are fewer to get nommed, which means fewer babby viruses getting borned. And CD4 cells dont have babbies, they get borned from other cells. So you have a steady supply of babby CD4 cells, but a declining number of babby viruses. Eventually, the HIV are nomming CD4 at the same rate that CD4 cells are being borned. In 1993, it was discovered that when this equilibrium was reached, there were still a fair amount of CD4 cells at any given time.

HIV wouldn't be much of a problem if that was the only way it killed CD4 cells. But it turns out that it also noms the mommy cells. But the mommy cells aren't all that tasty, so it noms them slowly. Fewer mommy cells, fewer babby CD4 cells, and eventually too few to stop AIDS-defining illnesses.