The distinguishing NS5-M114V mutation in American Zika virus isolates has negligible impacts on virus replication and transmission potential

• Published in: PLoS neglected tropical diseases Vol. 16; no. 5; p. e0010426
• Main Authors: Peng, Nias Y G, Amarilla, Alberto A, Hugo, Leon E, Modhiran, Naphak, Sng, Julian D J, Slonchak, Andrii, Watterson, Daniel, Setoh, Yin Xiang, Khromykh, Alexander A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2022; Public Library of Science (PLoS)
• Subjects: Amino acids; Analysis; Aquatic insects; Biological response modifiers; Biology and Life Sciences; Cells; Complications; Epidemics; Gene mutations; Genomes; Infections; Interferon; Medicine and Health Sciences; Methionine; Microbiological strains; Mosquitoes; Mutagenesis; Mutation; Neurological complications; NS5 protein; Nucleotide sequence; Outbreaks; People and Places; Proteins; Receptors; Replication; Saliva; Secretion; Stat2 protein; Strains; Transmission; Tropical diseases; Valine; Vector-borne diseases; Viremia; Virulence; Viruses; Zika virus; Australia; Asia; Pacific Islands
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0010426

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 but 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.