Researchers have discovered replication hubs for human norovirus, potentially paving the way for new antiviral drugs. The study, conducted by scientists at Baylor College of Medicine and the University of Texas MD Anderson Cancer Center, was published in Science Advances. Human norovirus is a significant cause of viral gastroenteritis worldwide, leading to approximately 685 million cases and around 212,000 deaths annually.
Dr. Soni Kaundal from Baylor College explained that viruses typically create "replication factories" within cells to produce new viruses. The research team found evidence suggesting that these replication hubs in norovirus are biomolecular condensates formed by liquid-liquid phase separation.
Kaundal noted, “We knew that these condensates are often initiated by a single viral protein capable of binding genetic material.” The team used bioinformatics to identify proteins in the human norovirus strain GII.4 with the potential to form such condensates. Their focus was on RNA-dependent RNA polymerase due to its propensity to form biomolecular condensates essential for viral replication.
Experimental studies confirmed that this polymerase forms dynamic liquid-like condensates under lab conditions, crucial for norovirus replication. Professor B.V. Venkataram Prasad stated, “The flexible region of this protein is critical for this process.”
Further investigations showed that similar condensates form in infected human intestinal cells using a cultivation system developed by Dr. Mary Estes's lab at Baylor in 2016. Estes commented on the findings: “This is a remarkable paper, and I was glad we could validate the findings in virus-infected cells.”
The study suggests these replication hubs might be common across most norovirus strains and offers insights into targeting them with antiviral treatments. Other contributors include Ramakrishnan Anish and others affiliated with Baylor College of Medicine and MD Anderson Cancer Center.
Funding for this research came from various grants including NIH grant P01 AI057788 and others provided by the Robert Welch Foundation and CPRIT.
