Zika virus(ZIKV)can infect a wide range of tissues including the developmental brain of human fetus.Whether specific viral genetic variants are linked to neuropathology is incompletely understood.To address this,we ha...Zika virus(ZIKV)can infect a wide range of tissues including the developmental brain of human fetus.Whether specific viral genetic variants are linked to neuropathology is incompletely understood.To address this,we have intracranially serially passaged a clinical ZIKV isolate(SW01)in neonatal mice and discovered variants that exhibit markedly increased virulence and neurotropism.Deep sequencing analysis combining with molecular virology studies revealed that a single 67D(Aspartic acid)to N(Asparagine)substitution on E protein is sufficient to confer the increased virulence and neurotropism in vivo.Notably,virus clones with D67N mutation had higher viral production and caused more severe cytopathic effect(CPE)in human neural astrocytes U251 cells in vitro,indicating its potential neurological toxicity to human brain.These findings revealed that a single mutation D67N on ZIKV envelope may lead to severe neuro lesion that may help to explain the neurovirulence of ZIKV and suggest monitoring the occurrence of this mutation during nature infection may be important.展开更多
基金supported in part by the following grants:Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29040301 to X.J.)National Key R&D Program of China(2016YFC1201000 to X.J.)+2 种基金Ministry of Science and Technology of China(2016YFE0133500 to X.J.)the National Natural Science Foundation of China(31770190 and 81925025 to CF.Q.)European Union Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement(734548 to X.J.)
文摘Zika virus(ZIKV)can infect a wide range of tissues including the developmental brain of human fetus.Whether specific viral genetic variants are linked to neuropathology is incompletely understood.To address this,we have intracranially serially passaged a clinical ZIKV isolate(SW01)in neonatal mice and discovered variants that exhibit markedly increased virulence and neurotropism.Deep sequencing analysis combining with molecular virology studies revealed that a single 67D(Aspartic acid)to N(Asparagine)substitution on E protein is sufficient to confer the increased virulence and neurotropism in vivo.Notably,virus clones with D67N mutation had higher viral production and caused more severe cytopathic effect(CPE)in human neural astrocytes U251 cells in vitro,indicating its potential neurological toxicity to human brain.These findings revealed that a single mutation D67N on ZIKV envelope may lead to severe neuro lesion that may help to explain the neurovirulence of ZIKV and suggest monitoring the occurrence of this mutation during nature infection may be important.
