Rapid evolution of enhanced Zika virus virulence during direct vertebrate transmission chains

Abstract

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.

The Ability of Zika virus Intravenous Immunoglobulin to Protect From or Enhance Zika Virus Disease

“…Beginning with an outbreak in 2013, our understanding of the risk and severity of ZIKV disease changed ( 17 ). Studies have suggested that the increase in ZIKV virulence is associated introduction of the virus into a naïve population combined with the ability of the virus to persist for extended periods in body fluids expanding the window for ZIKV to be sexually transmitted ( 18 – 20 ). Sexual transmission and mosquito associated infection increases the risk of fetal ZIKV infection leading to congenital Zika virus syndrome (CZS) ( 21 – 23 ).…”