What do viruses do inside cells?
As we head into winter in the Northern Hemisphere, as well as long nights and dreary weather, another certainty is that - soon - we’ll all be succumbing to this season’s circulating strains of colds and flu viruses. At the moment, we can’t do much about them - except treat the symptoms - because we don’t know the details of what going on when a virus gets into one of our cells. So finding viral “Achilles’ heels” that we can hit with drugs to trip up an infection is very tricky. Now though, Cambridge scientist Omer Ziv has found a cunning way to freeze an infecting virus in its tracks and then pull out the parts of the cell that the virus is interacting with so we can discover how it makes us ill and possibly where to focus our drug-developing activities. He spoke with Chris Smith...
Omer - We are interested in viruses. Viruses are those little creatures that go inside our bodies and make us ill. And we are interest to know how those viruses manipulate our cells, practically tell the cell: “stop everything you’ve been doing so far and start making more viruses”.
Chris - Yeah. Cause viruses are sort of like the pirates of the microbial world, aren’t they? They have to hijack our cells and turn them into virus factories because they’re so tiny they don’t have space inside the virus particle for any of the machinery that you need to make new viruses. They need one our cells to do that.
Omer - Yes, exactly. They enter our cells and manipulate whatever the cell is doing but we don’t know, essentially, how.
Chris - What have you therefore invented here? How does your technique shed light on that?
Omer - We’ve been developing a technique that enables us to freeze in time the virus infection and find out how viruses interact with the host on the molecular level.
Chris - Is that a bit like if I were to put a virus into a cell, wait a little while and then, as you say, freeze time and then look inside the cell and ask what bits of the virus are binding onto, or interacting with, or controlling what bits of the cell? So I can see what’s having a chemical conversation with what.
Omer - Yes, exactly. And once we find those interactions, assuming that part of them might be essential for the virus, we can think then of finding ways to target, to inhibit, interfere with those interactions and affect the virus life cycle.
Chris - How have you done this though? How do you do that freezing in time effect?
Omer - To do that we need to glue the interacting molecules together to fix those interactions and then extract information. We used small chemicals to enable us to link, to glue those interactions together and identify the interacting partners.
Chris - How do you make the glue set? How do you actually say right, now I want to freeze time and make that binding effect kick in?
Omer - The glueing starts whenever I treat the infected cells with those small chemicals that can enter the cell and glue physically the interacting molecules one to each other.
Chris - Are you saying then that if you can spot what these interactions are it might highlight to us, much more quickly than we would otherwise be able to discover them, potential, essential processes that the virus relies on to grow and make us unwell? And, therefore, you could engineer some way of either switching off that target or putting something into the cell that would stop that interaction and, therefore, it could block the virus?
Omer - Yes, exactly. We are interested both in the biology so the new technique might teach us how this virus has replicated inside the cells, and also understand whether those interactions are targetable and whether we use them for our development of new mediations.