Fragile X mental retardation protein is a Zika virus restriction factor that is antagonized by subgenomic flaviviral RNA

Certain mosquitoes can carry pathogens that are able to infect humans, including Zika and dengue viruses. Most people infected with Zika virus only develop mild symptoms, or no symptoms at all. But if the virus infects a pregnant woman, it can lead to miscarriage and other pregnancy complications, or cause severe birth defects in her unborn baby. Viruses must infect the cells of a host to multiply. To do so, they hijack the cellular machinery to make proteins needed to copy their genetic material and assemble new virus particles. The genetic material of Zika virus is made of ribonucleic acid (RNA). When the Zika virus infects cells, pieces of the virus RNA, known as subgenomic flavivirus RNAs (or sfRNAs for short), accumulate in the cell. Cells infected with dengue virus, which is closely related to the Zika virus, also accumulate sfRNA. Dengue sfRNA is known to bind to and inhibit the activity of specific proteins in cells that would otherwise block the virus from multiplying. Nonetheless, it is not clear whether the sfRNA from Zika virus performs a similar role. Soto-Acosta et al. searched for human proteins that could bind to Zika sfRNA and may affect the ability of the virus to multiply. The experiments showed that a protein known as FMRP, which, when faulty, is linked to a genetic condition that causes a range of developmental problems, binds to Zika sfRNA in human and mouse cells infected with Zika virus. FMRP inhibits the production of virus proteins in the cells and limits the ability of the virus to multiply. However, as Zika sfRNA gradually accumulates during infection, the sfRNA binds to FMRP and interferes with its activity, allowing the virus to multiply more efficiently. Soto-Acosta et al. also found that Zika sfRNA affects the ability of FMRP to regulate the production of other proteins that are normally found in cells. These findings suggest that the interference of the virus with FMRP may contribute to Zika disease in humans. Moreover, a mutant Zika virus unable to produce sfRNA could be developed into a vaccine to potentially prevent Zika.