Friday, July 06, 2007

HIV: Keeps getting more impossible-er

Im going to pretend to act shocked that no one, including Behe, cares to elaborate on his claims that HIV has evolved ' no protein binding sites — neither short linear peptide motifs nor any other — developed in a hundred billion billion (10 20) malarial cells. Or in HIV.' Or his original 'there have been no significant basic biochemical changes in the virus {HIV} at all.'

I gave one example to the contrary, HIVs vif gene, which figured out (sorry, personifying a virus) how to hijack humans anti-retroviral APOBEC protein for HIVs advantage.

Due to the loose language of his claim, the vif example does leave Behe wiggle room. How about something that goes above and beyond The Blessed Malaria argument? How about a 5 amino acid insertion (not just mutation from one amino acid to another) that changes a vital HIV structure? An insertion that alters a dTTP binding site?

Uh oh!!

Evolution of a novel 5-amino-acid insertion in the β3–β4 loop of HIV-1 reverse transcriptase

Reverse Transcriptase (RT) is the HIV protein that turns its RNA genome into DNA so it can be inserted into your genome. It is the target for anti-retrovirals like AZT. Now, mutations in RT to compensate for the presence of RT-inhibitors are common, and the most 'popular' mutations are well documented. Change an amino acid here, change an amino acid there, HIV becomes resistant to one drug or another (yes, weve even characterized mutational pathways to resistance, much to Behes dismay).

This particular insertion is completely novel to us, and the researchers wanted to know what kind of impact it had on viral fitness and resistance to RT-inhibitors. When they generated a virus identical to the ones with the insertion, but missing the insertion, the one with the insertion was only 3 times as resistant to RT-inhibitors. It doesnt appear to be that big of a deal... until you add a high concentration of RT-inhibitors. Suddenly, 3 times more fit becomes a huge advantage.

And of course, HIV kept evolving in this patient after the insertion. Completely new (seriously, havent seen these before) mutational pathways stepped up to increase the fitness of the RT resistant HIV even further. In ~10 days, HIV viruses with the 5 aa insertion went from making up 5% of the patients quasispecies to 20% of the quasispecies.

In sample 4A only 1 out of the 20 clones (5%) contained the insertion, while sample 4B revealed that 20% of the viral population harboured the insertion (4/20 clones). {Sample 4a collected at ~Day 235, 4B ~Day 245. ERV}
Oh dear. Not only did this real world HIV example exhibit a 'significant biochemical change', it did another Creationist Impossibility: virus went down a fitness valley (drug resistant HIV is usually less fit than wild type HIV, this example was no exception) to reach a higher fitness peak (drug resistant and a higher replicative capacity)*.

I bet theyre wrong, though. Im sure Behe is right.



* Now you and I know that in a real fitness landscape, down isnt always down and up isnt always up, and time is always a dimension, but we're talking about Creationist World and Creationist Fitness Landscapes. This is only a Creationist Impossibility, not an Evilutionary Impossibility.

9 comments:

Chris Harrison said...

Seriously Abbie, it creeps me out how exciting you make viruses.

Great post!

Chris Harrison said...

Oh, and I think this paper is very similar to the one your post covers, although I've not read past the abstract:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=509125

ERV said...

Theyre viruses! It takes conscious effort to make them not interesting!

Hey that paper does look similar (hehe only read the abstract thus far too).

Blake Stacey said...

Linked.

Snowcrash said...

Very good post, enjoyed reading it :)

ERV said...

Blake-- 5 years from now, Im going to post something on this topic, and I bet youll catch it. hehehe!!

Yay! Thanks snow!

Andrew Staroscik said...

Thank the intelligent designer himself that people like you are around to sing the praises of Behe's air tight arguments.

Very nice post.

Chris Noble said...

ERV seeing as you are remarkably troll free I feel obliged to give you some of the expected objections.

a) This "mutation" was obviously front loaded by the Designer.

b) This is not "natural" selection therefore it as actually evidence of Intelligent Design.

c) HIV has never been proven to exist

Just to annoy you I'll randomly alternate between all three so I can ignore all your responses to the other two.

VWXYNot? said...

Viruses are the coolest little bits of nucleic acid in the universe.