Abstract
Zika virus (ZIKV) is an emergent mosquito-borne member of the Flaviviridae family that was responsible for a recent epidemic in the Americas. ZIKV has been associated with severe clinical complications, including neurological disorder such as Guillain-Barré syndrome in adults and severe fetal abnormalities and microcephaly in newborn infants. Given the significance of these clinical manifestations, the development of tools and reagents to study the pathogenesis of ZIKV and to develop new therapeutic options are urgently needed. In this respect, the implementation of reverse genetic techniques has allowed the direct manipulation of the viral genome to generate recombinant (r)ZIKVs, which have provided investigators with powerful systems to answer important questions about the biology of ZIKV, including virus-host interactions, the mechanism of transmission and pathogenesis or the function of viral proteins. In this review, we will summarize the different reverse genetic strategies that have been implemented, to date, for the generation of rZIKVs and the applications of these platforms for the development of replicon systems or reporter-expressing viruses.
Highlights
Zika virus (ZIKV) is a member of the Flavivirus genus that belongs to the Flaviviridae family and is closely related to other mosquitoes-transmitted flaviviruses of public health relevance such as Dengue virus (DENV), Yellow fever virus (YFV), Japanese encephalitis virus (JEV) and West Nile virus (WNV) [2,3]
Viruses, flaviviruses replication occurs on virus-induced host cell membranes, mainly characterized by invaginations of the endoplasmic reticulum (ER) membrane termed vesicle packets, which serve as scaffold for anchoring the viral replication complexes [29,30,31]
In the last two years, several approaches based on the use of infectious RNA transcripts from full-length ZIKV cDNAs have been developed to overcome the toxicity problems associated with several sequences of ZIKV genome when amplified in bacteria
Summary
Zika virus (ZIKV) is a recently emerged mosquito-borne virus, which in 2016 was declared as an international public health emergency by the World Health Organization ZIKV vRNA is made of a positive single-stranded RNA molecule of approximately 10.8 kb with a single open translated by cap-dependent initiation producing a single polyprotein of approximately 3423 amino reading frame, flanked at the 5′- and 3′-ends by the viral untranslated regions (UTRs) (Figure 1B). The acid environment inside the endosome induces major conformational changes in the E glycoprotein that promote fusion of the viral and endosome membranes and the subsequent release of the viral genome into the cytoplasm of the infected cell. As other positive-stranded RNA viruses, flaviviruses replication occurs on virus-induced host cell membranes, mainly characterized by invaginations of the endoplasmic reticulum (ER) membrane termed vesicle packets, which serve as scaffold for anchoring the viral replication complexes [29,30,31]. The development of ZIKV reverse genetic systems provide investigators with a powerful tool for the development of vaccines and antivirals to counteract disease caused by this important human pathogen
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