Australian researchers report that a rabies virus protein changes shape and binds RNA to access liquid-like cellular compartments, offering a unifying explanation for how the virus exerts broad control with few genes. The work, published October 29, 2025, in Nature Communications, could inform future antivirals and vaccines, the team says.
A study led by scientists at Monash University and the University of Melbourne describes how the rabies virus phosphoprotein (P) gains a wide range of functions by switching conformations and binding RNA. In lab models, these properties allow the protein—particularly its P3 isoform—to interact with biomolecular condensates formed by liquid–liquid phase separation, providing access to cellular hubs that regulate key processes. The research was published in Nature Communications on October 29, 2025 (DOI: 10.1038/s41467-025-65223-y).
The findings help explain how rabies can do so much with so little genetic material. Rabies virus encodes five structural proteins—N, P, M, G and L—far fewer than the roughly 20,000 proteins in a human cell, yet it can manipulate antiviral defenses and other pathways. The International Committee on Taxonomy of Viruses and standard medical references confirm the five‑gene genome organization of rabies virus.
“Our study shows that shape changes and RNA binding give the P protein a remarkable range of functions,” said co‑first author Stephen Rawlinson. Co‑senior author Greg Moseley added that viruses like rabies are lethal in part because they take over multiple cellular systems, including those tied to protein production and immune defense. “They hijack the machinery that makes proteins, and disable the defenses that normally protect us,” he said in a Monash‑provided summary. Paul Gooley of the University of Melbourne said RNA binding enables the protein to move among the cell’s liquid‑like compartments, “turning the cell into a highly efficient virus factory,” according to the same account. The quotes were provided via a university release disseminated by ScienceDaily.
The authors report that P3—but not the full‑length P1—binds RNA, and that this interaction correlates with the protein’s ability to engage phase‑separated cellular structures, challenging the traditional “modular” view of viral protein multifunctionality. Instead, they propose that long‑range conformational regulation, together with RNA binding, underpins how one viral gene product can access many host pathways.
While the experiments centered on rabies, the researchers suggest similar strategies may operate in other high‑consequence viruses such as Nipah and Ebola. They caution that translating these insights into therapies will require more work, but argue that targeting protein conformational dynamics or RNA‑binding interfaces could be a path toward antivirals or improved vaccines.
The collaboration included Monash University; the University of Melbourne; the Australian Nuclear Science and Technology Organisation’s Australian Synchrotron; the Peter Doherty Institute for Infection and Immunity; CSIRO’s Australian Centre for Disease Preparedness; and Deakin University.
