부산대학교 도서관

During 2015–2016, outbreaks of Zika virus (ZIKV) occurred in Southeast Asia and the Americas. Most ZIKV infections in humans are asymptomatic, while clinical manifestation is usually a self-limiting febrile disease with maculopapular rash. However, ZIKV is capable of inducing a range of severe neurological complications collectively described as congenital Zika syndrome (CZS). Notably, the scale and magnitude of outbreaks in Southeast Asia were significantly smaller compared to those in the Americas. Sequence comparison between epidemic-associated ZIKV strains from Southeast Asia with those from the Americas revealed a methionine to valine substitution at residue position 114 of the NS5 protein (NS5-M114V) in all the American isolates. Using an American isolate of ZIKV (Natal), we investigated the impact of NS5-M114V mutation on virus replication in cells, virulence in interferon (IFN) α/β receptor knockout (Ifnar-/-) mice, as well as replication and transmission potential in Aedes aegypti mosquitoes. We demonstrated that NS5-M114V mutation had insignificant effect on ZIKV replication efficiency in cells, its ability to degrade STAT2, and virulence in vivo, albeit viremia was slightly prolonged in mice. Furthermore, NS5-M114V mutation decreased mosquito infection and dissemination rates and had no effect on virus secretion into the saliva. Taken together, our findings support the notion that NS5-M114V mutation is unlikely to be a major determinant for virus replication and transmission potential. Author summary: Zika virus (ZIKV) emerged to cause outbreaks in Southeast Asia and the Americas during 2015–2016. However, the scale of outbreaks in Southeast Asia were significantly smaller compared to epidemic in the Americas. A methionine to valine amino acid mutation at residue position 114 of the NS5 protein (NS5-M114V) is hypothesized to influence the epidemic outcomes of ZIKV, which led to the large-scale epidemic that occurred in the Americas. By analyzing infection of mammalian and mosquito cells, IFNα/β receptor knockout (Ifnar-/-) mice and Aedes aegypti mosquitoes with engineered ZIKV isolates containing either methionine or valine at residue position 114 of the NS5 protein, we demonstrated that the NS5-M114V mutation did not affect virus replication efficiency and STAT2 degradation in cells, virulence in mice, or virus secretion into the mosquito saliva. The NS5-M114V mutation slightly prolonged viremia in Ifnar-/- mice and reduced mosquito infection rate. Collectively, our findings suggest that the NS5-M114V mutation is unlikely to have significantly influenced the ZIKV epidemic in the Americas. [ABSTRACT FROM AUTHOR]