Dengue and Zika virus capsid proteins bind to membranes and self-assemble into liquid droplets with nucleic acids

AMBROGGIO, ERNESTO E.; NAVARRO, GUADALUPE S. COSTA; SOCAS, LUIS BENITO PÉREZ; BAGATOLLI, LUIS A.; GAMARNIK, ANDREA V.

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Año: 2021 vol. 297

0021-9258

engue virus (DENV) and Zika virus (ZIKV) capsid proteins efficiently recruit and surround the viralRNAat the endoplasmic reticulum (ER) membrane to yield nascent viral particles. However, little is known either about the molecular mechanisms by which multiple copies of capsid proteins assemble into nucleocapsids (NCs) or how the NC is recruited and wrapped by the ER membrane during particle morphogenesis. Here, we measured relevant interactions concerning this viral process using purified DENV and ZIKV capsid proteins, membranes mimicking the ER lipid composition, and nucleic acids in in vitro conditions to understand the biophysical properties of the RNA genome encapsidation process. We found that both ZIKV and DENV capsid proteins bound to liposomes at liquid-disordered phase regions, docked exogenous membranes, and RNA molecules. Liquid-liquid phase separation is prone to occur when positively charged proteins interact with nucleic acids, which is indeed the case for the studied ca