For a virus, a compact genome neatly packaged in a coat of proteins, survival is all about invading a cell, taking over the protein-making machinery to replicate itself and then spreading to other cells. To do this successfully, it might seem self-evident that the entirety of a virus’s small genome would have to be inside an infected cell. A new study recently published in eLife, however, overturns that assumption.

Not only are some viruses split into multiple segments that infect host cells separately, but as researchers in France have now discovered, those fractured viruses can flourish with their genomes scattered like puzzle pieces across a multitude of host cells. Something — presumably, the diffusion of molecules among the infected cells — allows complete viral particles to replicate, self-assemble and infect anew.

“You can get all of the necessary gene products together to produce new viruses in a cell that doesn’t actually have all the gene segments in it,” explained Christopher Brooke, a virologist at the University of Illinois at Urbana-Champaign.

“A classical view in virology assumes that the viral replication cycle occurs within individual cells,” said Anne Sicard, the lead author of the new study and a plant pathologist at the French National Institute for Agricultural Research (Institut National de la Recherche Agronomique, or INRA) in Montpellier. But in the case of this “multipartite” virus that she and her colleagues examined, “it seems that this is not true. The segments infect cells independently and accumulate independently in the plant host cells.” She added, “It really shows that the virus doesn’t work at a single-cell level, but at a multicellular level.”

Multipartite viruses have been known for over half a century, when researchers realized that a virus could be composed of two or more independent pieces, all of which were vital for infection. One piece might be necessary for making essential viral enzymes, for instance, while the other would be needed to make the capsule in which the viral particles (or virions) are packaged and transported to other cells.

But being multipartite carries considerable risks. Parts of the genome can easily be lost or left behind, dooming the rest by breaking the cycle of infection. Because the segments are frequently found in different proportions — some may be common, while others are rare — the rare ones can be lost especially easily.

Scientists have therefore wondered about multipartite viruses since they discovered them. “Why on earth would a virus do this? Why would you separate your genome? What are the advantages to having these segments that are packaged separately?” asked Mark P. Zwart, an evolutionary virologist at the Netherlands Institute of Ecology.

To explore these questions, theoreticians developed models to predict the circumstances under which this multipartite lifestyle would evolve from a more typical viral ancestor, all built on the assumption that the full set of viral segments had to coinfect one cell. But the results were perplexing. A study from 2012 concluded that, whatever the benefits of multipartition might be, the disadvantages were so great that a virus with more than four segments should be impossible. Yet some multipartite viruses, like the faba bean necrotic stunt virus (FBNSV), were known to have as many as eight segments, each carried in a different particle. Theoretically, it couldn’t have evolved. What could explain its existence?

“We thought that the way we conceptualize these viruses must be wrong,” said Stéphane Blanc, a plant virologist at INRA and the senior author of the new study. They decided to verify the key assumption that all the segments must be together within a cell for the infection to work. “It was not done before because it was so evident that they have to be together that no one actually tested it,” he said.

What they found when they scrutinized FBNSV infections blew them away. By tagging two viral segments at a time with different colored fluorescent probes, the team could see that the full complement of viral segments was absent from the vast majority of individual host plant cells they examined. Furthermore, the researchers showed that a protein required for viral replication was present in cells that did not have the genome segment coding for it.

From this, they inferred that the virus particles must be sharing gene products — either messenger RNA molecules or proteins — among cells, so that each particle could replicate and package itself into a capsule to spread. How exactly those necessary components are shared across plant cells isn’t fully understood, but Blanc and his team are looking into it. The answer may involve the plasmodesmata, networks of microscopic canals that extend through plant cell walls and allow adjacent cells to share other proteins.