Structural Insight Into The Zika Virus Capsidencapsulating The Viral Genome

Flaviviruses are important emerging and reemerging human pathogens,including West Nile virus(WNV),Dengue virus(DENV),yellow fever virus(YFV)and Zika virus(ZIKV).Particularly,Zika virus(ZIKV),outbreak began in 2015.Except mild clinical symptoms such as fever,myalgia,and rash,in Brazil,with the outbreak of ZIKV,neonatal microcephaly and Guillain-Barré syndrome and other nerves systemic diseases has also increased significantly.Zika virus has been found to cause severe neurological pathologies such as neonatal microcephaly and Guillain-Barré syndrome.This poses an important threat to world health and safety,draws a attention in the world,so it is imminent to study antiviral.The flavivirus capsid(C)protein is one of the structural proteins of the flavivirus,it plays a critical role in encapsulation of the RNA genome and formation a nucleocapsid.It has been pointed out that the C protein of flavivirus is involved in the assembly of viral RNA and the formation of mature virus particles,and the virus cannot form infectious particles in the absence of C protein.In addition,it has been found that C protein binds to double-stranded DNA to inhibit host RNA silencing and thereby suppressing the host's immune response.Therefore,C protein is also an attractive drug design target.However,the role of the flavivirus C protein during encapsulation of the viral RNA genome is largely unknown.Here,we report the 2.0-? crystal structure for the dimer of ZIKV C protein.Each protomer contains a long,structured loop at its N-terminus,resulting in a much larger dimerization surface than other flavivirus C proteins.Analyzing the crystal structure of the protein C dimer,it was found that a positively charged path that wraps around the entire ZIKV C dimer has been identified and appears to be essential for nucleic acid binding.EMSA assay reveal that the positive surface charge of the protein C dimer is important to appeared to bind nucleic acids,and the positive residues on the path are conserved across the species as well.We propose a model for the ZIKV and other flavivirus C proteins that encapsulate the viral genome.Our model shows that the single-stranded viral RNA genome likely wraps around individual C dimers to form a “beads on a string” ribonucleocomplex structure.