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• Zika virus RNAs aid in the establishment of productive infection and evasion of host cell antiviral responses. • Alterations in m6A methylation of Zika virus RNA can have significant impact on virus production. • Zika virus has a low codon usage bias but a nucleotide composition with strong under-representation of CpG and UpA. • An abundant, non-coding subgenomic flavivirus RNA (sfRNA) is produced during Zika virus replication. • Analysis of 95 individual Zika virus 3’UTR sequences indicates nucleotide variation in predicted non-structured regions. Zika virus (ZIKV; family Flaviviridae ; genus Flavivirus ) is a pathogenic mosquito-borne RNA virus that currently threatens human health in the Americas, large parts of Asia and occasionally elsewhere in the world. ZIKV infection is often asymptomatic but can cause severe symptoms including congenital microcephaly and Guillain-Barré syndrome. The positive single-stranded RNA genome of the mosquito-borne ZIKV requires effective replication in two evolutionary distinct hosts – mosquitoes and primates. In addition to some of the viral proteins, the ZIKV genomic RNA and functional RNAs produced thereof aid in the establishment of productive infection and the evasion of host cell antiviral responses. ZIKV has evolved to contain a nucleotide composition and RNA modifications, such as methylation and the formation of G-quadruplexes that allow effective replication in both hosts. Furthermore, a number of host factors interact with the viral genome to modulate RNA replication. Importantly, the ZIKV genome produces non-coding subgenomic flavivirus RNA (sfRNA) due to stalling of host 5′- 3′ ribonucleases on viral RNA structures in the 3′ untranslated region (UTR). This sfRNA (sfRNA) exerts important proviral functions such as antagonizing the innate interferon response and RNA interference. Here, we discuss the ZIKV genomic RNA and functional RNAs thereof to assess their significance during ZIKV infection. Understanding the details of the ZIKV infection cycle will aid in the development of effective antiviral strategies and safe vaccines.
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Göertz et al. (2017) studied this question.
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