New insights into our understanding of a curious type of virus have been claimed by physicists in China, Japan and the US – but some scientists are not convinced. The team modified the established “SIR” model of how viruses spread to try to explain the surprising success of multipartite viruses. These viruses have genetic material that is split amongst multiple viral particles, with each particle needing to infect the same cell for replication to occur. While some multipartite virus experts welcome the efforts of the physicists, they have questioned the biological accuracy of the modified model.
Numerical models are the bread and butter of theoretical physics and their application in biophysics has helped scientists glean important insights into biological processes. But it can be extremely difficult to turn the intricacies of nature into equations and on occasion crucial details can be lost in translation between biology and physics. According to some virus experts, this problem has cropped up in research described in a recent paper in Physical Review Letters, where much to the excitement of experts in the field, physicists have tried to tackle the baffling behaviour of the multipartite virus.
For most viruses, it only takes one infection for a virus to replicate, but multipartite viruses are weird. Their genetic material is split between different particles and need multiple infection events to occur. This seems disadvantageous and so the evolutionary success of multipartite viruses, primarily in plant and fungi hosts, has long baffled scientists.
Static interactions
Now, Yi-Jiao Zhang and colleagues at Lanzhou University, Tokyo Institute of Technology and Indiana University have used epidemiological models to evaluate a core factor that differs between plants and animals. Plants usually stay in one place and therefore interact only with their neighbours. In contrast animals usually move around in space and have more dynamical interactions with others.
“Intuitively in a dynamic network with connections that change rapidly, you expect spread to be faster and broader. But we found that the multipartite viruses had a lower colonization threshold in the static networks, meaning that in plants the virus spreads easier than in animals, says Zhang. “This is very unusual for an epidemic model.”
Zhang and colleagues used a minimal model of a bipartite virus in two types of host networks – one that shuffles its connections, mimicking the changing interactions between animals, and a static network mimicking the relatively fixed interactions between plants. They began with a classic epidemiology model that defines viral hosts as being in one of three states: these are susceptible (S) when no virus particles are present in the host; infectious (I) with both parts of the virus present; and recovered (R) or dead from infection. They extended this “SIR” model to include a fourth latent (L) state where a host is infected with one type of virus particle but not the other. In this L state they cannot infect other individuals.
“Difficult to justify”
It is this L state that has sparked debate in the research community. Susanna Manrubia is a physicist at the Spanish National Centre for Biotechnology in Madrid who has studied multipartite viruses for over a decade. She says, “Unfortunately, this L state is difficult to justify. Once the genomic fragments enter the cell, they are exposed to the action of proteins that degrade polynucleotides different from the DNA of the host (of the plant, in this case). Therefore, there is degradation in the unreplicated genomic material of the virus that affects L states,”
This concern is echoed by Mark Zwart of the Netherlands Institute of Ecology, who studies the ecology and evolution of viruses and bacteria. “This latent state doesn’t really mesh with what we know about the biology of these viruses,” he says.
Zhang acknowledges these concerns but points to studies that her team believes supported the possibility that multipartite viruses survive in host cells for a sufficiently long time.
Manrubia disagrees, pointing out that replication is occurring in each of the experimental studies highlighted and therefore she does not think that they support a long-lived L state. “The problem is not trivial and, since experimental approaches to viruses are often highly intricate, there are important details that may have been inadvertently overlooked,” she says.
Important applications
Despite their reservations, both Manrubia and Zwart voiced their excitement that these types of models are starting to be applied to multipartite viruses.
Manrubia is pleased to see the bigger ecological picture of how host dynamics impacts multipartite virus spread being considered, “I have the hunch that their [multipartite viruses’] competitive strength relies on ecological features, precisely of the type this paper addresses.”
The flu fighters
Zwart thinks the techniques used in Zhang’s research will be very useful in pinning down how multipartite viruses spread from cell to cell within a single plant host.
To spread within a host plant, viruses move from an infected cell to the adjacent cells using the existing communication and contact routes between cells. Perhaps these restrictions on virus spread are the reason why multipartite viruses have been evolutionary so successful in plants. Zwart is hopeful that Zhang and colleagues will apply their methods to find out. “Plant viruses have really different lifestyles, and if they use these type of models at the within host level then it might be more relevant and could capture those sort of dynamics,” said Zwart.
