The Biology journal of the Public Library of Science, in its April 2009 edition, has a fascinating paper that suggests that we humans, within that part of our DNA often referred to as “junk DNA”, may have the necessary instructions to make compounds that prevent the HIV-1 retrovirus from attacking human cells.
There is a class of small anti-microbial molecules (peptides) produced by mammals, called defensins, that are active against a broad range of pathogenic organisms. There are three classes of these defensins in primates, based on their chemical structure: alpha, beta, and theta. The theta defensins are the most recently discovered, and it was originally thought that they only occurred in old-world primates, such as rhesus monkeys. They act primarily by preventing viruses from entering the body’s cells.
The researchers found that human DNA contains the genetic encoding for these theta defensins, but they are not expressed because the genetic sequence contains a premature “stop” codon; these are called pseudo-genes. (You can think of these termination codons as being like STOP signes that indicate the end of a gene, just as text files in ancient personal computer systems were terminated by a CTL-Z character.) When the researchers generated a sample of human promyelocytic cells with “repaired” genes, the cells were able to produce the structures of the theta defensins. The researchers were also able to confirm the anti-HIV activity of these compounds in vitro.
This is potentially an exciting result. It is made even more interesting, as the researchers observe, by the fact that certain antibiotics can induce the production of these defensins:
Furthermore, we exploited the ability of aminoglycoside antibiotics to read-through the premature termination codon within retrocyclin transcripts to produce functional peptides that are active against HIV-1.
It’s also worth noting that many genetic disorders are the result of similar “premature” termination codons in the relevant genes, so a technique which can, essentially, ignore them during DNA-directed synthesis might have wide application.
It is interesting to speculate on how we humans lost the ability to make these compounds, which at least some of our close genetic relatives still have, But this discovery potentially opens up a new avenue of prevention of HIV infection.