Negligible contribution of M2634V substitution to ZIKV pathogenesis in AG6 mice revealed by a bacterial promoter activity reduced infectious clone

Scientific Reports
Fanfan ZhaoGang Long

Abstract

ZIKV has emerged as a significant human pathogene for the severe neurological complications, including Guillain-Barré(GBS) syndrome in adults and a variety of fetal abnormalities such as microcephaly. A stable and efficient infectious clone of Brazilian ZIKV isolate is required to study pathogenesis of epidemic ZIKV and virus evolution impact on it. Here we successfully constructed infectious cDNA clone on an early Brazilian isolate by eliminating the activity of predicted bacterial promoter in 1-3000 nt of ZIKV genome, leading to a stable infectious cDNA clone (pZL1). pZL1 derived virus could infect different cell lines and cause lethal effect to AG6 mice. We further investigated the role of a recent emerged substitution in NS5 (M2634V). We found that a reverse mutation (V2634M) caused negligible effect on the ZIKV viral genome replication and infectious progeny production in multiple cell culture systems. Additionally, this mutation did not alter the pathogenesis feature and virulence of ZIKV in AG6 mice. In summary, our results present another robust infectious ZIKV clone from Brazilian isolate and provide evidences to support that M2634V single mutation did not alter virus life cycle in cell culture and pathogenesis in AG6 ...Continue Reading

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Citations

Oct 17, 2018·The Journal of General Virology·Lindomar José PenaAntonio Carlos de Freitas
Jan 9, 2019·Nature Reviews. Microbiology·Zhong-Yu LiuCheng-Feng Qin
Nov 6, 2018·Viruses·Ginés Ávila-PérezLuis Martínez-Sobrido

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Datasets Mentioned

BETA
KU321639.1
KU963796

Methods Mentioned

BETA
PCR
in vitro transcription
electrophoresis

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