Association between Guillain-Barré syndrome and Zika virus infection – Authors' reply

Fontanet, Arnaud; Cao-Lormeau, Van-Mai; Dub, Timothée; Mallet, Henri‐Pierre; Ghawche, F

doi:10.1016/s0140-6736(16)30773-5

Cited by 6 publications

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After the large Brazilian outbreak started in late 2014, active transmission was reported in approximately 60 countries and territories globally [7]. Contrasting the Yap island outbreak, which was characterized by cases with relatively mild dengue-like symptoms the outbreaks in French Polynesia and Brazil were associated with an unusual proportion of serious neurological disorders such as microcephaly in newborn infants [8] and Guillain-Barré syndrome in adults [9–10]. The public-health emergency raised by ZIKV [11] stimulated efforts to build up human in vitro and animal in vivo models to understand how ZIKV causes developmental abnormalities [12–13], and to develop a vaccine.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular arrangement of the full-length Zika virus NS5

et al. 2019

View full text Add to dashboard Cite

Zika virus (ZIKV), a member of the Flavivirida e family, has emerged as a major public health threat, since ZIKV infection has been connected to microcephaly and other neurological disorders. Flavivirus genome replication is driven by NS5, an RNA-dependent RNA polymerase (RdRP) that also contains a N-terminal methyltransferase domain essential for viral mRNA capping. Given its crucial roles, ZIKV NS5 has become an attractive antiviral target. Here, we have used integrated structural biology approaches to characterize the supramolecular arrangement of the full-length ZIKV NS5, highlighting the assembly and interfaces between NS5 monomers within a dimeric structure, as well as the dimer-dimer interactions to form higher order fibril-like structures. The relative orientation of each monomer within the dimer provides a model to explain the coordination between MTase and RdRP domains across neighboring NS5 molecules and mutational studies underscore the crucial role of the MTase residues Y25, K28 and K29 in NS5 dimerization. The basic residue K28 also participates in GTP binding and competition experiments indicate that NS5 dimerization is disrupted at high GTP concentrations. This competition represents a first glimpse at a molecular level explaining how dimerization might regulate the capping process.

show abstract