Tuesday 23 August 2011

HIV therapies: new challenges, new hopes

HIV is a very sneaky virus that has developed many strategies of evading the immune system. One of the strategies is direct transmission of viral particles from cell to cell. What other viruses normally do, is they infect a cell, use it to multiply themselves in the thousands and make the cell release the new viral particles ready to infect further cells. But cells infected by HIV also do something else. They create tiny channels by which they connect their content with the content of another cell. And HIV uses these channels like a motorway to quickly travel to a new cell and establish a new replication centre.
In a recently published study (1), scientists hypothesised that this highway route of transmission might not only be faster and more efficient in infecting new cells, but also increase the chances of the virus escaping the action of anti-retroviral drugs. Here’s what their theoretical idea was.
If an infected cell releases viruses to the environment, the new virus, before infecting the next cell, drifts around in the solution randomly, as HIV has no mechanism to home onto target cells. It’s a little bit like standing with your mouth open when it’s snowing: even though there are thousands and thousands of snowflakes around, only a small number will make it on your tongue. Let’s call this way a drifting virus infection. However, imagine there was a tube that you put in your mouth that has a large funnel on the other side. Hundreds of snowflakes would find it much easier to travel directly through the tune into your mouth. Let’s call this funnelled infection. Now, let’s change the analogy and think of the virus as wasps invading your house and travelling straight onto the doughnuts on your kitchen table, and your anti-wasp spray will be the anti-retroviral drug. When you get the odd wasp every now and then (drifting infection), you can easily fend them off with your spray. But when you get hundreds of them barging through your window in an instant (funnelled infection), chances are, you will miss a few and they will reach the doughnuts. In the viral terms, it means escaping the anti-retroviral drugs and establishing an replication centre in a new cell. So this was the scientists’ theory, but how did they test it? Quite simply. They took some cells and mixed them with a solution of the virus, and either mixed in some drugs or not. As expected, many cells got successfully infected in the absence of the drug, while in its presence, very little did. For the second part of the experiment, they mixed some cells which were already infected by the virus and were red with some uninfected cell, which were green. And again, they did it in the presence or absence of the drug. After some time they removed all the red cells, and counted how many of the green ones were infected. And consistently with their theory – even though the drug decreased the number of green cells getting infected, this reduction was nowhere near as successful as that observed in the first part of the experiment. The wasps flew in in their hundreds and often managed to escape the spray.
AIDS is one of the worst pandemics to have ever affected the world. There is no cure, and the development of a successful vaccine is still in infant stages. Currently, the only thing that can be done is to use anti-retroviral therapy to control the virus and minimise the damage it does to patient’s body. The research I mentioned here can be seen as both bad news and good news. Bad news, because it shows the weakness of the current anti-retroviral therapy. Good news, because it showed how important this alternative way of virus transmission is. Now that we realise it, we can try to develop new drugs, which will close the connections between the cells. Or, using our metaphor, close the window and not let any wasps in. There’s a new challenge, a new hope.

1. Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy

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