Flaviviridae viruses cause various human diseases, but there is no proper treatment. During infection, their core proteins enter the host cell’s nucleus to help the virus replicate.
Researchers from Juntendo University have found that a protein called importin-7 is critical to moving these viral proteins into the nucleus. This discovery could lead to new treatments for flavivirus-related diseases.
Flaviviridae viruses, like Dengue, Zika, and West Nile, are significant threats, causing severe diseases such as Guillain–Barré syndrome and dengue fever. Dengue alone infects about 390 million people yearly. Despite the rising global risk, there is still no effective treatment. While these viruses were once thought to stay in the cell’s cytoplasm, recent research shows that their core proteins enter the nucleus, essential for replication.
A study has identified a protein called importin-7 (IPO7) that carries these viral proteins into the nucleus, offering a potential target for new treatments. Researchers confirmed this by removing the IPO7 gene using CRISPR technology.
“Our study found that IPO7 is a carrier that helps Flaviviridae core proteins enter the cell nucleus. When IPO7 was removed, the core proteins couldn’t enter the nucleus,” explains Prof. Okamoto.
Researchers then tested how removing IPO7 affected virus production by infecting cells with flavivirus. Cells without IPO7 produced fewer viral particles, even though both cell types had similar virus levels inside. This shows that IPO7 is essential for creating new viral particles, especially in the later stages of the virus’s life cycle. The study suggests that blocking IPO7’s role could help reduce the virus’s impact.
Effective treatments for Flaviviridae viruses, like dengue, are needed since no specific medications are available. Prof. Okamoto explains that current dengue treatment focuses on supportive care, but developing antiviral drugs or vaccines is crucial. Other viruses like JEV and ZIKV also lack treatments.
In earlier research, Prof. Okamoto’s team found compounds that block flavivirus core proteins from entering the nucleus, reducing viral replication. This study further identifies IPO7 as a critical target for stopping the virus. Prof. Okamoto hopes this finding will lead to the development of effective anti-flavivirus drugs.
Journal reference :
- Yumi Itoh, Yoichi Miyamoto, et al., Importin-7-dependent nuclear translocation of the Flavivirus core protein is required for infectious virus production. PLOS Pathogens. DOI: 10.1371/journal.ppat.1012409.