Debunking myths on genetics and DNA

Thursday, August 23, 2012

The mystery of the Delta antigen

Now I feel like I should write a spy-fiction story on the delta antigen... Maybe I will... But for now, here's the real story.

When in the mid '70s a group of patients in Turin, Italy, presented a particularly virulent form of Hepatitis B (HBV), medical researchers thought they had found a new subtype of the virus. Liver biopsies from infected patients revealed a new antigen, which was thought to be a new protein encoded by HBV. There was a mystery to solve, though: why was the new antigen (called Delta) found only in certain HBV infected patients but not others?

A collaboration between the University of Turin and the NIH revealed, thanks to experiments conducted on chimpanzee, that the Delta antigen was indeed a new virus, the Hepatitis D virus (HDV). Why was it only found in HBV-infected patients? Because HDV is a satellite virus, in other words, it can only infect a liver cell if the HBV virus is also present in the cell.

Similarly to viroids, the HDV genome is a circular single-stranded RNA and, even though not as small as a viroid genome, with its ~1700 bases, it's still much smaller than the average viral genome. It utilizes the cellular RNA polymerase in order to replicate, and HBV envelope proteins in order to propagate. HDV and HBV coinfection is rare in the western world, but quite common in sub-Saharan Africa, the Middle East, and the northern part of South America, where it is mostly transmitted among drug users (like the other hepatitis viruses, it is a blood-borne disease).

So, how did HDV develop in relation to HBV? Given the close resemblance that HDV has with viroids, Taylor and Pelchat [1] report as a likely hypothesis that it had originated from a plant virus (plant viruses can be disseminated in human digestive tracts) and infected the liver of an HBV-infected animal. It could also have originated directly from HBV through a random replication error. As the researchers conclude,
"Furthermore, discovery of the widespread occurrence of HDV-like ribozymes and their possible relationship to retrotransposition further demonstrates that some of what appeared to be unique properties of HDV and viroids are barely the tip of a major biological iceberg."

[1] John Taylor, & Martin Pelchat (2012). Origin of hepatitis δ virus Future Medicine DOI: 10.2217/fmb.10.15

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