Cellular Housekeeping could block HIV

31 January 2013

Interview with

Professor Beth Levine, University of Texas Southwestern Medical Centre

Researchers have announced that they've come up with a new way to block the growth of viruses and this might even offer us a cure against the common cold.  

Beth Levine from the University of Texas Southwestern Medical Centre has discovered a molecule that can activate a system called autophagy- the cells used to remove waste including any viruses, and even bacteria that are also trying to grow in the cell.  

And she got the idea from HIV which actually turns off this system.  So, turning it back on hinders virus growth, and what's more, the discovery might even hold the key to treating degenerative brain diseases like Huntington's disease too.

Beth -   When we embarked upon this study, we were interested in trying to understand how viruses disarms the essential mechanism that cells use to defend themselves against viruses.

Chris -   What is that?

Beth -   That is a cellular pathway called autophagy.  In very simple terms, you can view it as a cellular garbage disposal mechanism.  Basically, that way of "cleaning up a trash" as we say in the US and getting rid of all the harmful or unwanted things inside the cell such as damaged organelles or bacteria, or viruses that have gotten inside the cell or miscoded proteins that can cause disease.

Chris -   And so, cells can just turn this process on or increase the rate at Microscopy image of a herpes virus.which it happens if they need to do deal with an accumulation or some feat of trash, as you put it?

Beth -   Yes, so all cells do this all the time.  It is essential for cellular survival.  When they're confronted by different kinds of stress they do so and viruses and intercellular bacteria have found ways to outsmart that.

Chris -   Do they need to outsmart the process because if you've got a virus trying to grow in a cell, then the viruses causing the cell to accumulate various things which were actually going to turn into ultimately bits of virus and were the cell to throw those away would obviously hamper the ability of the virus to grow?  So, by inhibiting this disposal system, the viruses optimising or improving the efficiency which is able to grow in a cell.

Beth -   Exactly, yes.

Chris -   And so, what viruses have evolved to have strategies that mean they can turn this off?

Beth -   So far, the viruses that we know about that turn this off are HIV-AIDS, influenza virus, and several different herpes viruses.

Chris -   So, the fact that it's so common in so many different types of virus tells us that this is obviously really important for the ability of viruses to grow efficiently in cells.  And so, were you to turn the tables and find a way to turn it back on again, so the viruses can't block it, you might potentially have a whole new way to treat lots of these infections?

Beth -   Exactly.  It's turning out that many different viruses as well as many different bacteria have multiple different strategies to block autophagy.  Even the same virus can have many proteins that block autophagy, so that I think illustrates just how important it is for their own survival and if we can prevent the virus from outsmarting the host cell and bypass the block that the virus puts, pathogy that could be a strategy for treating viral infections.

Chris -   Have you managed to find a way to stop viruses from turning off this system?

Beth -   Well the peptide that we recently discovered which we reported in the article that came out in Nature today is composed of 18 amino acids from the autophagy protein beclin-1, one of the essential proteins that's necessary for autophagosomes to form.

Chris -   These are the structures in cells that do the breaking down?

Beth -   Right and it can increase autophagy in virally infected cells, and we have shown in cell culture systems that it can inhibit the replication of HIV, and intracellular bacteria called diphtheria and to mosquito-borne viruses, chikungunya virus, and west Nile virus.  And we also showed in animal studies in mice infected with chikungunya and west Nile virus that administration of this peptide could reduce levels of infectious virus in their tissue and reduce mortality.

Chris -   So, you have this short little protein which when you put it onto cells does appear to have this very powerful anti-viral effect and it seems from what you're saying to actually work against a range of different viruses.  So, does this mean that a.) we could find a way of doing this in pill form and that ultimately, we will be getting a cure for the common cold?

Beth -   Well, I couldn't claim that we have the answer yet, but this is something that people then kind of seek out for decades or centuries, but I think that the goal would be,  as you're eluding to, I think having the sequence of the peptide that we have and further understanding of its mechanism will enable collaborators in the industry to develop a small molecule that could mimic the actions of its peptide.  And the goal would be to move this into human trials and see whether it could be a cure for different viruses and other diseases.

Chris -   Just to finish off and the key is in what you just said 'other diseases'.  There are a range of other diseases that are nothing to do with viruses, we don't necessarily think, but they do cause rubbish to build up inside cells, these neurodegenerative diseases like Huntington's.  Now, if you could activate or soup-up autophagy in those cells, so that of that accumulating rubbish which we think leads to the destruction of nerve cells and causes the disease, does that mean we might also here have an answer to dealing with a whole raft of these nerve-disabling disorders?

Beth -   I would like to be cautious in saying that there are a lot of steps that we need to take to first, confirm the safety of this approach in animal models.  But in principle, I think there's a strong likelihood that that could work.

Chris -   Beth Levine from the University of Texas Southwestern Medical Centre and that study was published this week in the journal Nature.

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