Viruses that spread in swarms

26 April 2019

Interview with 

Stephane Blanc, University of Montpellier

MULTIPARTITE-VIRUS

Multipartite virus replicating different components in different cells

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The majority of viruses that we encounter consist of a single particle that contains all of the genetic information required to stage an infection successfully. But that’s not true of all viruses, especially some of those that crop up in plants, and Chris Smith hears about one such "multipartite virus" - faba bean necrotic stunt virus - that replicates different bits of the virus in different cells from the University of Montpellier's Stephane Blanc...

Stephane - These viruses are called tripartite, which means that each piece of information is packaged separately in a distinct virus particle. So what you call the virus is in fact a small population of virus particles. The whole information is never contained in a single virus particle for these viruses.

Chris - That’s Stephane Blanc and, yes, you heard that correctly - the virus he studies - called “Faba bean necrotic stunt virus” - effectively operates as an infectious “swarm” where different viral particles contain different genetic elements and they have to share the resources that each encodes and produces to enable all of the viral particles to replicate and sustain the population as a whole. Obviously this comes at a cost…

Stephane - Theoretical studies concluded that if the virus has more than three or four pieces for the genome information - and the virus we work with has actually eight - and they concluded that these viruses should not evolve. This should not work. So that was the basis of our whole program, that we work with a virus that should not exist.

Chris - Indeed, if you’re relying on gene products from another viral component that might not even be in the same cell as you, that doesn’t sound like a recipe for success, does it.

Stephane - This conclusion that it should not exist is based on a strong assumption: that all the pieces must be together within a cell for the system to work. So we decided to just verify this. Are all the pieces together in an individual cell. Or is this just a sort of dogma that may not be true in our case? We decided to localize each individual piece in an infected host. And for this, because each piece of the genome has a different sequence, we can make probes that are specific for one piece. Those probes can be fluorescent with different colors. And then we can see whether the colors are always together, or whether the colors are separate; which would mean that the different pieces do not need to be together.

Chris - But this virus is split up into 8 distinct, independently-replicating pieces, and with present technology it’s not easy to look for all 8 at the same time. So Stephane’s solution has been to look for pairs of genome components that are present in the same cell to work out how likely it would be statistically to end up with all 8 pieces in one cell at the once.

Stephane - If one piece of genome is together with another piece of genome in, let's say, 30% of the cases; and that this other piece of genome you can show in another experiment that is present with, again, another piece of genome in 30% of the cases; then you can calculate the probability to find a cell with all 8 segments. So this is a statistical inference. And this type of estimation predicts that we probably have 1% of the infected cell that may contain all eight segments. So they are extremely rare.

Chris - In fact, they’re far too rare to sustain the population. And it’s not just a copy-number effect where the team are seeing cells with a detectable amount of just a couple of genome segments at one point in time: they’ve followed the infection for hours in these cells and never seen other genome segment signatures develop later.

Stephane - All the cells contain some piece of the genome. And these pieces of information, although they are not with all the pieces, they are replicated. So it means that in those cells where the genome is not complete, the genetic information is replicated. So the replication cycle occurs even in cells where the genome is not complete. And that's the discovery.

Chris - So a cell infected with just part of the virus can nonetheless still replicate that component. But this would require components made by bits of the virus that the cell doesn’t actually have! So how does it do it?

Stephane - What we call the piece of information of the genome. They are genes that produce something that the virus needs to build baby viruses. So in different cells, different pieces of information produce this material. and it must be exchanged in between the cell. So that's what we believe, that the virus, one piece of information is sending away its product to complement the other pieces of information in other cells. And for this, either the virus is opening gates, communication between cells so that it can exchange product between cells containing different pieces of information; or the virus uses natural cell-to-cell communication of the host. This we don't know yet. We have to investigate the details of the mechanism in the future.

Chris - So there's still work to do to establish how the population of infected cells are networked together to share resources in this way. There's also the obvious question of why does this virus do this at all.

Stephane - Many viruses are in just one piece. So these are the canonical view we have on viruses, derived from the canonical viruses, which are in one piece. No-one clearly understands why these viruses in several pieces actually do it. But our contribution is that before our contribution, people in the community were wondering, how is this possible, right. Because they cannot efficiently bring all pieces together in an individual cell. We show that they don't have to do it and that the system can function. So what we address is more that the cost of doing that is not so high. But we do not address that benefit. So the benefit remains a mystery.

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