Genomic and phenotypic analyses suggest moderate fitness differences among Zika virus lineages

Summary

RNA viruses have short generation times and high mutation rates, allowing them to undergo rapid molecular evolution during epidemics. However, the extent of RNA virus phenotypic evolution within epidemics and the resulting effects on fitness and virulence remain mostly unknown. Here, we screened the 2015-2016 Zika epidemic in the Americas for lineage-specific fitness differences. We engineered a library of recombinant viruses representing twelve major Zika virus lineages and used them to measure replicative fitness within disease-relevant human primary cells and live mosquitoes. We found that two of these lineages conferred significant in vitro replicative fitness changes among human primary cells, but we did not find fitness changes in Aedes aegypti mosquitoes. Additionally, we found evidence for elevated levels of positive selection among five amino acid sites that define major Zika virus lineages. While our work suggests that Zika virus may have acquired several phenotypic changes during a short time scale, these changes were relatively moderate and do not appear to have enhanced virulence or transmission during the epidemic.

Zika virus Infectious Clones

Clade	ZIKV Genome Locus	Gene	AA location	Ancestor AA	Mutant AA	Comments
AM-A	3534	NS1	349	M	V	Revert V-->M
AM-B (Paraiba_01) No Changes
AM-C	8631	NS5	322	I	V
	10301	NS5	878	D	E
AM-D	8631	NS5	322	I	V
	10090	NS5	808	T	I
	10301	NS5	878	D	E
AM-E	3534	NS1	349	M	V	Revert V-->M
	2788	NS1	100	G	A
	6327	NS3	572	M	L
	9240	NS5	525	R	C
AM-F	3534	NS1	349	M	V
	428	C	107	D	E
AM-G	3534	NS1	349	M	V	Revert V-->M
	428	C	107	D	E
	3459	NS1	324	R	W
	10164	NS5	833	T	A
AM-H	345	C	80	I	T
	3534	NS1	349	M	V	Revert V-->M
AM-I	345	C	80	I	T
	3534	NS1	349	M	V	Revert V-->M
	8467	NS5	267	V	A
AM-J	3534	NS1	349	M	V
	2788	NS1	100	G	A
	6327	NS3	572	M	L
	4731	NS3	40	V	I
	9240	NS5	525	R	C
Pre-AM-1	3534	NS1	349	M	V	Revert V-->M
	8007	NS5	114	M	V	Revert V-->M
Pre-AM-2	3534	NS1	349	M	V	Revert V-->M
	523	prM	17	S	N	Revert S-->N
	6363	NS3	584	Y	H
	8007	NS5	114	M	V	Revert V-->M
Pre-AM-3	3534	NS1	349	M	V	Revert V-->M
	8007	NS5	114	M	V	Revert V-->M
	523	prM	17	S	N
	6363	NS3	584	Y	H
	3070	NS1	194	V	A

Disclaimer. Please note that this data is still based on work in progress and should be considered preliminary. If you intend to include any of these data in publications, please let us know – otherwise please feel free to download and use without restrictions. We have shared this data with the hope that people will download and use it, as well as scrutinize it so we can improve our methods and analyses. Please contact us if you have any questions or comments – we’ll buy beers for #ResearchParasites that spot flaws and faults in the data and come up with improvements!

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Andersen Lab
The Scripps Research Institute
La Jolla, CA, USA
data@andersen-lab.com