Scientists Discover a Vulnerability in HIV's Protective Shell
The discovery offers a new target for future treatments.
A team of researchers from the UK's Medical Research Council (MRC) has discovered a key feature used by the HIV virus to infect healthy cells without giving itself away and triggering a corresponding immune response. The work, which is described this week in Nature, exposes a new target for anti-HIV treatments while potentially offering new insights into improving the delivery of existing drugs.
HIV is what's technically known as a retrovirus. It consists of genetic material in the form of RNA and a protective protein coating called a capsid. Its process of infection involves the virus first entering the healthy target cell, and, from within the cell's cytoplasm, producing DNA from RNA, which goes on to integrate itself into the cell's own genome. The now-host cell will behave in accordance with the virus's genetic programming—that is, it will start producing whatever proteins the new DNA tells it to. Most viruses, however, do something like the opposite of this and use their own DNA to produce RNA, which is inserted into the target cell where it will itself command the production of proteins. This difference is where the "retro" comes from.
Part of what makes retroviruses weird is that they're able to get away with this DNA production at all. Cells have alarm systems of sorts that are meant to detect foreign DNA and eventually trigger an immune response. Moreover, retroviruses have to come up with the nucleotides required to build DNA from RNA. (A refresher: RNA molecules are tiny bits of genetic material coding for specific proteins, while DNA molecules are like genetic data centers containing the whole genetic description of an organism. DNA contains the templates needed for many sorts of RNA.)
Somehow, HIV pulls off its retro act and this has remained somewhat of a mystery. According to the new paper, the answer lies in tiny pores (below) found throughout the virus's protective capsid. The pores, which open and close in a manner similar to that of the iris in an eye, allow the virus to take in nucleotides while keeping its true nature hidden from the invaded cell until it's too late.
"We used to think that the capsid came apart as soon as the virus entered a cell but now realise that the capsid protects the virus from our innate immune system," explains senior author Leo James in an MRC statement. "The channels we've discovered explain how the fuel for replication gets into the capsid to allow the viral genome to be made."
The MRC group did more than just identify the virus's top secret DNA delivery channels—they tested out a preliminary method for blocking them. As it turns out, the compound hexacarboxybenzene does a great job of this because it competes for the same binding sites within the virus that the nucleotides do. So, rather than receiving shipments of DNA raw materials through its pores, the HIV virus just gets this weird chemical. And, given high enough concentrations, the hexacarboxybenzene was able to completely stop the virus's DNA construction. Without the ability to make DNA, HIV is kind of just an inert wad of protein and nucleic acid.
This doesn't quite mean that hexacarboxybenzene is a readymade HIV wonderdrug. Its usage here seems to be more a proof of concept that these pores can indeed be blocked at all. While this will likely point the way toward new and better treatments, it may also help researchers improve current HIV drugs, many of which function to block the process of RNA to DNA conversion as well.