Wednesday, August 12, 2009

Fighting HIV: It's What's Inside That Counts (Really)

So researchers are finding another approach to battling HIV that makes use of genes we already have? Cool. Here's an excerpt from the paper that came out a few months ago:
A group of scientists led by Nitya Venkataraman and Alexander Colewhether wanted to try a new approach to fighting HIV - one that worked with the body's own immune system. They knew Old World monkeys had a built-in immunity to HIV: a protein called retrocyclin, which can prevent HIV from entering cell walls and starting an infection. So they began poring over the human genome, looking to see if humans had a latent gene that could manufacture retrocyclin too. It turned out that we did, but a "nonsense mutation" in the gene had turned it off at some point in our evolutionary history.
The team found a way to use a compound called aminoglycosides, which itself can cause errors when RNA transcribes information from DNA to make proteins. But this time, the aminoglycoside error would work in their favor: It would cause that RNA to ignore the nonsense mutation in the junk gene, and therefore start making retrocyclin again. In preliminary tests, their scheme worked. The human cells made retrocyclin, fended off HIV, and effectively became AIDS-resistant.
Wow. Seriously, that's amazing. Unfortunately, judging by some of the comments on the article, I think a few people might interpret this the wrong way. I'm taking a look at the paper, and I want to make a few points:

First, this is not a cure for HIV. It's a possible preventative mechanism.

Second, this has only been tried in cultured cells, I believe. It hasn't been done in a whole human, it has not gone through any clinical trials. The authors of the paper only speculate that a topical vaginal cream could possibly help prevent sexual transmission of the virus. It's just a possible avenue for future research.

Now for the science stuff (be aware that I do not know everything about everything. I am a bio major, but I'm still just an undergrad, so feel free to correct me wherever I'm wrong - constructively, of course).

One reader states that we should be careful since the mutation "is apparently not so nonsense as to affect the entire human race, surviving all evolutionary steps since its appearance." No, not exactly.
The scientists are not judging the quality of the mutation or its effect on the population." Nonsense mutation" is a scientific term. A nonsense mutation creates a stop codon, a sequence of three nucleotides that cause a ribosome to stop translating messenger RNA (the intermediate between DNA and protein).

Next, this is not exactly I Am Legend, as one commenter so charmingly alleges. Although the researchers mutated the DNA to find out whether the gene could possibly work without the termination codon in the middle, that is not part of the suggested treatment for people. The part that applies to prevention in the body deals with translation of the gene. What you're doing is skipping over the nonsense stop codon that prevents the ribosome from translating the gene all the way through (from mRNA into protein). The DNA remains unchanged, and even the mRNA is unaffected. In fact, I'm pretty sure we don't even have a way to change all the DNA in our bodies - gene therapy is not yet possible.

Lastly, some aminoglycosides are antibiotics. Part of what they do is disrupting proofreading during DNA replication in bacterial cells and inhibiting translation. In eukaryotes (which include animals such as us), the effect is to make ribosomes hiccup and sort of skip past a termination codon. They can be used to help a cell overcome nonsense mutations in disease-causing genes. According to the authors, aminoglycosides have been researched in this capacity before.

*Edit: I'm still reading about this, and I should point out that retrocyclins are not specific to HIV, they just protect against that kind of virus.

For some more info, check out Ed Yong over at Scienceblogs. He has a better explanation of everything (as he should, since he's an award-winning science writer and I am a mere undergrad).

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