High transmissibility and fetal pathogenicity of recent Zika virus strains from the African lineage

Abstract

SummaryThe global emergence of Zika virus (ZIKV) in the last decade revealed the unprecedented ability for a mosquito-borne virus to cause congenital birth defects such as microcephaly. A puzzling aspect of ZIKV emergence is that all human outbreaks and birth defects to date have been exclusively associated with the Asian ZIKV lineage, despite a growing body of laboratory evidence pointing towards higher transmissibility and pathogenicity of the African ZIKV lineage. Whether this apparent paradox reflects the use of relatively old African ZIKV strains in most laboratory studies is unclear. Here, we experimentally compared the transmissibility and pathogenicity of seven low-passage ZIKV strains representing the recently circulating viral genetic diversity. We found that recent African ZIKV strains largely outperformed their Asian counterparts in mosquito transmission kinetics experiments, which translated into a markedly higher epidemic potential in outbreak computer simulations. In addition, African ZIKV strains were significantly more lethal than Asian ZIKV strains in immunocompromised adult mice. Finally, prenatal infection of immunocompetent mouse embryos with an African ZIKV strain resulted in embryonic death whereas it caused microcephaly with Asian ZIKV strains. Together, our results demonstrate the high epidemic potential and pathogenicity of recent ZIKV strains from Africa. Importantly, they also imply that the African ZIKV lineage could more easily go unnoticed by public health surveillance systems than the Asian ZIKV lineage due to its propensity to cause fetal loss rather than birth defects.

Neuroinvasiveness of the MR766 strain of Zika virus in IFNAR-/- mice maps to prM residues conserved amongst African genotype viruses

“…generally more neurovirulent [20,25], one might speculate that they would more reliably induce miscarriage and/or fetal demise [123,[142][143][144], thereby reducing the likelihood of births of viable infants with CZS (S16 Fig) [29,140,141,145,146].…”

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

“…As a result, extensive research efforts have aimed to understand whether there are mutations that have contributed to the severity of the ZIKV outbreak in the Americas. Mounting evidence indicates that African-lineage and American-sublineage ZIKV are generally more transmissible than other Asian lineage ZIKVs (Aubry et al, 2020; Calvez et al, 2018; Liu et al, 2017; Pompon et al, 2017; Roundy et al, 2017; Weger-Lucarelli et al, 2016). Further, a panel of mutations present in American-sublineage ZIKV, but not other Asian-lineage ZIKV, were shown to enhance transmission by Aedes aegypti mosquitoes, as well as replication and virulence in mouse models (Liu et al, 2020; Shan et al, 2020).…”