A revolutionary discovery has shaken up our most basic assumptions about how viruses replicate.
There are some theories in biology which are widely accepted as truth. The refinement of our genomes through natural selection, for example, or the “central dogma” which dictates the multi-step processing of DNA instructions to functional protein. An example from virology is the basic understanding of how a virus – simply a selection of genes encased in a capsule – replicates inside its host. Or so we thought.
Now, a revolutionary discovery by Stephane Blanc at the University of Montpellier threatens to change everything, exposing our fundamental assumptions about viral life cycles as exactly that: assumptions.
The textbook, high-school-biology-curriculum description of how viral replication usually works, goes as follows: the virus infiltrates a host and gains access to a cell. Inside that cell the virus commandeers the manufacturing machinery of its host for its own nefarious purposes, making copy after copy of itself. The collection of unruly offspring burst free from the cell, destroying it in the process, and each moves on to a new unwitting target.
But Stephane Blanc, working with the Faba bean necrotic stunt virus (FBNSTV), has shown that this is not necessarily always the case.
FBNSTV is unusual in several ways. It is a “multipartite virus” which means that instead of keeping its collection of genes in one capsule, they are distributed across eight. These eight capsules move as a kind of colony through their hosts, and each one is required for the set of instructions needed to copy the virus to be complete. Intriguingly, though, Blanc’s group have now demonstrated that FBNSTV spends its life cycle distributed across different cells. In fact, the different capsules which make up the virus need never rendezvous in the same location at all.
The group made the discovery by engineering the different capsules to fluoresce with different colours. When they observed the fluorescence under the microscope they noticed over time that the different capsules only very rarely appeared in the same cells. Upon seeing this, “we were jumping and running around the lab,” Blanc says. “But we were also scared about it being a mistake. We took six years to verify it.”
This was initially a mystifying prospect. With the genetic instructions fragmented in this way, how could it be possible for the different capsules to replicate – each one missing the information split between the other seven?
Further research has revealed that the virus gets around this problem by setting up a type of distribution system between the different cells. Each capsule hijacks host machinery to manufacture its own product, which is transported to the other cells housing its seven capsular counterparts. In this way, although each capsule only has a part of the instructions, it gains access to the products encoded by the entire set. In essence, the virus exists only as this complex, distributive network.
This idea is entirely new to virology. “It’s pretty rare that you see a paper come out like that, that’s so sort of conceptually groundbreaking that it really kind of changes in really fundamental way how you think about how viruses exist,” says Christopher Brooke, who researches virology at the University of Illinois.
Multipartite viruses do not infect humans, and only very rarely infect animals – mainly focussing their efforts on plants and fungi. Because of this, Blanc notes a distinct lack of interest for his niche topic in the wider field. “I lecture on several virology courses, and even people in Ph.D. programs haven’t heard of them,” he says. “They’re everywhere, but because they’re mainly on plants, no one cares.”
If we can be sure of anything, it’s that his research will generate some much-deserved attention for this long-neglected organism.