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Zika virus prM protein contains cholesterol binding motifs required for virus entry and assembly

To successfully infect host cells and produce virions, Zika virus (ZIKV), like other enveloped viruses, relies on cellular lipids. However, how the interactions between viral proteins and lipids contribute to the viral life cycle remains poorly documented. Here, this collaborative work between the lab of Prof. Ralf Bartenschlager at the University of Heidelberg (Germany) and the iWays team at IVPC involved the use of reverse genetic methods, photo-affinity labeling assays, and atomistic molecular dynamics simulations in combination with chemo-proteomic and bioinformatics analyses. These approaches identified two functional cholesterol-binding motifs in the transmembrane domain of the viral pre-M protein. The loss of association between pre-M and cholesterol impacts both ZIKV entry and assembly. We propose a model in which the membrane-resident M protein of ZIKV facilitates lipid-cholesterol exchange during viral entry into endosomes and, together with cholesterol, creates a platform for virion assembly. In summary, we identify a bifunctional role for prM in the ZIKV life cycle by mediating viral entry and virus assembly in a cholesterol-dependent manner.

Read all about the results in the article published in the journal Nature Communications (November 2023)