Science News

HIV reveals clue to new antiviral agent

Thu, 31st Jan 2013

Chris Smith

Studying a substance produced by the human immunodeficiency virus (HIV-1) has revealed a powerful new therapeutic "anti-viral avenue". HIV Viruses

Writing in Nature this week, University of Texas Southwestern Medical Center scientist Beth Levine and her colleagues were examining how a factor called "Nef" contributes to the virulence of HIV.

They found that it locks onto and inactivates a protein called beclin-1, which, under normal circumstances, activates the cellular equivalent of a waste disposal system.

Such a system, called autophagy, is potentially bad for viruses because it would lead to them and their products being chewed up inside cells, which is why HIV has evolved a way to stop it.

The Texas-based team discovered that the HIV-1 Nef locks onto just one part of the beclin-1 protein, so they produced a soluble, synthetic version of this small region. Administered to cells, it powerfully activated the autophagy process and inhibited the growth of HIV in culture.

Even better, it also worked against two other viruses the team tested, chikungunya and West Nile Virus, including in experimentally infected animals, and even against the bacterium Listeria monocytogenes, which invades cells, hence its susceptbility to this treatment.

This approach therefore represents and exciting new way to combat viral, and even some bacterial infections.

But more exciting still is that since certain neurodegenerative diseases, including Huntington's Disease, are in part caused by a build-up of pathological protein material inside cells, activating this waste-degrading autophagy pathway could help to treat these diseases too.

"I am cautiously optimistic that this approach really could work," Levine says.


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It sounds a lot like computer viruses which are often programmed to disable the antivirus programs. 

So, the idea is to flood the cells with this binding site, giving the virus false targets to bind to?  Assuming that one can get the protein fragments into the cells.

Perhaps also non protein drugs could be produced to bind this viral protein.

If this one protein is so critical for pathogens to bind to, I could imagine an approach to gene therapy in which the protein itself is altered, and thus the diseases that attack that protein would need to re-evolve to attack the modified protein.  Potentially it could make humans or livestock much more disease resistant.

Would there be a version of the beclin-1protein/gene from other animals, perhaps even non-mammals that would be equally effective, but difficult for human or livestock diseases to attack, without bringing in the risk of more zoonotic diseases?  And, thus one could splice the different version of the gene into the genome. CliffordK, Thu, 31st Jan 2013

"The Texas-based team discovered that the HIV-1 Nef locks onto just one part of the beclin-1 protein, so they produced a soluble, synthetic version of this small region."

Whilst this is really interesting I can't help but wonder how long it will take HIV to worm its way around this. It binds to a 'small region' of a protein receptor. How long until it mutates to bind to a different region of the same protein? This is obviously having a direct impact on the survival of HIV, it will introduce a selection pressure and HIV is extremely responsive to such things. schneebfloob, Thu, 31st Jan 2013

It might,
However, that may mean that the virus would have to develop a whole new protein from scratch for the new binding site, something that would not be easy to do.

That would not be nearly as easy for the virus to do as modifying one of its own proteins so that it is no longer a target for a drug.

In fact, that would be an advantage of using natural proteins to make the fake receptors as it would be impossible to for the virus to differentiate between the real and fake receptors.  If a drug was used to block the HIV-1 Nef binding agent, then it might be possible for the HIV-1 Nef to curcumvent the drug and still bind to beclin-1.

Another possible adaptation would be for the virus to start over-producing its receptor blocker to overwhelm the "fake" receptors. CliffordK, Thu, 31st Jan 2013

Actually, it's more clever than that; because the virus is switching down the rate of autophagy within the cell by deactivating an activating molecule. What the beclin-derivative peptide does is de-repress the autophagy rate, increasing the processing and virus dismantling. So it a positive effect on cell physiology, rather than a direct anti-viral effect. chris, Tue, 19th Feb 2013

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