Hacking Swine Flu
One interesting consequence of reading this Nature article, and having access to the virus sequence, is that I now know how to modify the virus sequence to probably make it more deadly.
Here’s how:
The Nature article notes, for example, that variants of the PB2 Influenza gene with Glutamic acid at position 627 in the sequence has a low pathogenicity (not very deadly). However, PB2 variants with Lysine at the same position is more deadly. Well, let’s see the sequence of PB2 for H1N1. Going back to our NCBI database:
601 QQMRDVLGTFDTVQIIKLLP
621 FAAAPPEQSRMQFSSLTVNV
641 RGSGLRILVRGNSPVFNYNK
As you can see from the above annotation, position 627 has “E” in it, which is the code for Glutamic acid. Thankfully, it’s the less-deadly version; perhaps this is why not as many people have died from contracting H1N1 as the press releases might have scared you into thinking. Let’s reverse this back to the DNA code:
621 F A A A P P E Q S R
1861 tttgctgctg ctccaccaga acagagtagg
As you can see, we have “GAA” coding for “E” (Glutamic acid). To modify this genome to be more deadly, we simply need to replace “GAA” with one of the codes for Lysine (“K”), which is either of “AAA” or “AAG”. Thus, the more deadly variant of H1N1 would have its coding sequence read like this:
621 F A A A P P K Q S R
1861 tttgctgctg ctccaccaaa acagagtagg
^ changed
There. A single base-pair change, flipping two bits, is perhaps all you need to turn the current less-deadly H1N1 swine flu virus into a more deadly variant.
Theoretically, I could apply a long series of well-known biological procedures to synthesize this and actually implement this deadly variant; as a first step, I can go to any number of DNA synthesis websites (such as the cutely-named “Mr. Gene”) and order the modified sequence to get my deadly little project going for a little over $1,000. Note that Mr. Gene implements a screening procedure against DNA sequences that could be used to implement biohazardous products. I don’t know if they specifically screen against HA variants such as this modified H1 gene. Even if they do, there are well-known protocols for site-directed mutagenesis that can possibly be used to modify a single base of RNA from material extracted from normal H1N1.
[Just noticed this citation from the Nature article: Neumann, G. et al Generation of influenza A viruses entirely from cloned cDNA. Proc. Natl Acad. Sci. USA 96, 9345-9350 (1999). This paper tells you how to DIY an Influenza A. Good read.].
Adaptable Influenza
OK, before we get our hackles up about this little hack, let’s give Influenza some credit: after all, it packs a deadly punch in 3.2kbytes and despite our best efforts we can’t eradicate it. Could Influenza figure this out on its own?
The short answer is yes.
In fact, the Influenza virus is evolved to allow for these adaptations. Normally, when DNA is copied, an error-checking protein runs over the copied genome to verify that no mistakes were made. This keeps the error rate quite low. But remember, Influenza uses an RNA architecture. It therefore needs a different mechanism from DNA for copying.
It turns out that Influenza packs inside its virus capsule a protein complex (RNA-dependent RNA polymerase) that is customized for its style of RNA copying. Significantly, it omits the error checking protein. The result is that there is about one error made in copying every 10,000 base pairs. How long is the Influenza genome? About 13,000 base pairs. Thus, on average, every copy of an Influenza virus has one random mutation in it.
Some of these mutations make no difference; others render the virus harmless; and quite possibly, some render the virus much more dangerous. Since viruses are replicated and distributed in astronomical quantities, the chance that this little hack could end up occurring naturally is in fact quite high. This is part of the reason, I think, why the health officials are so worried about H1N1: we have no resistance to it, and even though it’s not quite so deadly today, it’s probably just a couple mutations away from being a much bigger health problem.
https://www.bunniestudios.com/blog/?page_id=1932