Health Science & Technology

Major breakthrough in the fight against HIV? Researchers identify molecule ‘hijacked’ by virus

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In what may represent a significant step forward in defeating HIV, researchers have identified what they believe to be the molecule the virus exploits when it infects human cells. 

The research which was published in the online journal for the biomedical sciences eLife centres on the small molecule inositol hexakisphosphate (IP6) which researchers believe the HIV virus may ‘hijack’ when first infects its human host. The virus then uses IP6 to shield itself from the immune system as it releases its viral payload into the host’s system.

The virus’ cells are already protected by a protein shell called a capsid container, but researchers now believe the virus uses IP6 to bolster this defence. This discovery, if it proves to be correct, may explain why HIV is so difficult to combat.

“For as long as it has been studied, the HIV capsid has been known to be highly unstable on its own,” structural virologist David Jacques from UNSW in Australia explained to ScienceAlert. “This has led to theories that maybe its lack of stability is somehow important to infection. With our discovery of IP6, we now know that during infections the HIV capsid is never ‘on its own’. It is always exposed to IP6, which dramatically stabilises the core of the virus.”

the HIV capsid has been so difficult to study as a result of its fragility

IP6 helps HIV collect viral components into complete packages known as virions, a fact that biologists have known for some time. What was unknown until now was just how it does this and how crucial IP6 is in HIV’s lifecycle. The difficulty in studying capsids comes from their tendency to crumble very quickly when isolated.

The new research indicates that the reason the capsid deteriorates so quickly in the lab is because it is being isolated from IP6.  The hijacked molecule helps the capsid container to stabilise itself from collapse, sometimes for up to 20 hours. When this support is removed at the molecular level, the capsid is unstable and quickly crumbles.

The knowledge that this is the cause of capsid collapse means that going forwards researchers can use IP6 to stabilise the protein container longer in order to study it deeper.

“Now that we know that IP6 is always present during normal infections, we can add this compound to stabilise the capsid in the test tube,” Jacques explains. “This opens up whole new avenues of research focused on understanding how the capsid works because we now have time to study it.”

Jaques and his team were able to make this breakthrough thanks to a new microscopy technique which utilises fluorescence. This enabled the team to monitor the breakdown of the capsid container in real-time. By monitoring thousands of individual virions the team could assess which other compounds effected its protective protein layer.

IP6 gives the virion time to collect more genetic material

Using this method the team discovered that IP6 binds to pores in the capsid strengthing it. This increases the amount of new viral DNA the virion is able to accumulate by a significant factor, perhaps up to 100 times that of an unstrengthened virion. This is a significant boost for a virus such as HIV.

As always with developing research, the results should be viewed cautiously, but researchers now hope that the HIV viruses dependance on IP6 can be utilized in the development of effective treatment methods. The key to deteating HIV may lie in turning its key strength against it.


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