RT Journal Article SR Electronic T1 Rapid evolution of enhanced Zika virus virulence during direct vertebrate transmission chains JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.10.23.353003 DO 10.1101/2020.10.23.353003 A1 Kasen K. Riemersma A1 Anna S. Jaeger A1 Chelsea M. Crooks A1 Katarina M. Braun A1 James Weger-Lucarelli A1 Gregory D. Ebel A1 Thomas C. Friedrich A1 Matthew T. Aliota YR 2020 UL http://biorxiv.org/content/early/2020/10/23/2020.10.23.353003.abstract AB Zika virus (ZIKV) has the unusual capacity to circumvent natural alternating mosquito-human transmission and be directly transmitted human-to-human via sexual and vertical routes. The impact of direct transmission on ZIKV evolution and adaptation to vertebrate hosts is unknown. Here we show that molecularly barcoded ZIKV rapidly adapted to a mammalian host during direct transmission chains in mice, coincident with the emergence of an amino acid substitution previously shown to enhance virulence. In contrast, little to no adaptation of ZIKV to mice was observed following chains of direct transmission in mosquitoes or alternating host transmission. Detailed genetic analyses revealed that ZIKV evolution in mice was generally more convergent and subjected to more relaxed purifying selection than in mosquitoes or alternate passages. These findings suggest that prevention of direct human transmission chains may be paramount to resist gains in ZIKV virulence.Competing Interest StatementThe authors have declared no competing interest.