Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes

Yang Liu, Jianying Liu, Senyan Du, Chao Shan, Kaixiao Nie, Rudian Zhang, Xiao Feng Li, Renli Zhang, Tao Wang, Cheng Feng Qin, Penghua Wang, Pei-Yong Shi, Gong Cheng

Research output: Contribution to journalArticle

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Abstract

Zika virus (ZIKV) remained obscure until the recent explosive outbreaks in French Polynesia (2013-2014) and South America (2015-2016). Phylogenetic studies have shown that ZIKV has evolved into African and Asian lineages. The Asian lineage of ZIKV was responsible for the recent epidemics in the Americas. However, the underlying mechanisms through which ZIKV rapidly and explosively spread from Asia to the Americas are unclear. Non-structural protein 1 (NS1) facilitates flavivirus acquisition by mosquitoes from an infected mammalian host and subsequently enhances viral prevalence in mosquitoes. Here we show that NS1 antigenaemia determines ZIKV infectivity in its mosquito vector Aedes aegypti, which acquires ZIKV via a blood meal. Clinical isolates from the most recent outbreak in the Americas were much more infectious in mosquitoes than the FSS13025 strain, which was isolated in Cambodia in 2010. Further analyses showed that these epidemic strains have higher NS1 antigenaemia than the FSS13025 strain because of an alanine-to-valine amino acid substitution at residue 188 in NS1. ZIKV infectivity was enhanced by this amino acid substitution in the ZIKV FSS13025 strain in mosquitoes that acquired ZIKV from a viraemic C57BL/6 mouse deficient in type I and II interferon (IFN) receptors (AG6 mouse). Our results reveal that ZIKV evolved to acquire a spontaneous mutation in its NS1 protein, resulting in increased NS1 antigenaemia. Enhancement of NS1 antigenaemia in infected hosts promotes ZIKV infectivity and prevalence in mosquitoes, which could have facilitated transmission during recent ZIKV epidemics.

Original languageEnglish (US)
Pages (from-to)482-486
Number of pages5
JournalNature
Volume545
Issue number7655
DOIs
StatePublished - May 25 2017

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Aedes
Culicidae
Proteins
Amino Acid Substitution
Disease Outbreaks
Zika Virus
Interferon alpha-beta Receptor
Polynesia
Cambodia
Flavivirus
South America
Valine
Inbred C57BL Mouse
Alanine
Meals

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Liu, Y., Liu, J., Du, S., Shan, C., Nie, K., Zhang, R., ... Cheng, G. (2017). Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. Nature, 545(7655), 482-486. https://doi.org/10.1038/nature22365

Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. / Liu, Yang; Liu, Jianying; Du, Senyan; Shan, Chao; Nie, Kaixiao; Zhang, Rudian; Li, Xiao Feng; Zhang, Renli; Wang, Tao; Qin, Cheng Feng; Wang, Penghua; Shi, Pei-Yong; Cheng, Gong.

In: Nature, Vol. 545, No. 7655, 25.05.2017, p. 482-486.

Research output: Contribution to journalArticle

Liu, Y, Liu, J, Du, S, Shan, C, Nie, K, Zhang, R, Li, XF, Zhang, R, Wang, T, Qin, CF, Wang, P, Shi, P-Y & Cheng, G 2017, 'Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes', Nature, vol. 545, no. 7655, pp. 482-486. https://doi.org/10.1038/nature22365
Liu Y, Liu J, Du S, Shan C, Nie K, Zhang R et al. Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. Nature. 2017 May 25;545(7655):482-486. https://doi.org/10.1038/nature22365
Liu, Yang ; Liu, Jianying ; Du, Senyan ; Shan, Chao ; Nie, Kaixiao ; Zhang, Rudian ; Li, Xiao Feng ; Zhang, Renli ; Wang, Tao ; Qin, Cheng Feng ; Wang, Penghua ; Shi, Pei-Yong ; Cheng, Gong. / Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. In: Nature. 2017 ; Vol. 545, No. 7655. pp. 482-486.
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