Evolution of Zika virus in <i>Rag1</i>-deficient mice selects for unique envelope glycosylation motif mutants that show enhanced replication fitness.

ABSTRACT: N-linked glycosylation of flavivirus envelope proteins is widely viewed as being required for optimal folding, processing and/or transit of envelope proteins, and the assembling virons, through the endoplasmic reticulum (ER) and the Golgi. Zika virus (ZIKV) has a single N-linked envelope glycan located adjacent to the fusion loop. Herein we show that independent serial passage of ZIKV_Natal in Rag1 ^-/- mice for 223 or 386 days generated two unique envelope glycan-deficient mutants, ZIKV-V153D and ZIKV-N154D, respectively. Surprisingly, these mutants grew to titres ∼1 to 2.6 logs higher than the glycosylated parental ZIKV_Natal in Vero E6 cells and human brain organoids. RNA-Seq of infected organoids suggested that this increased replication fitness was

SUBMITTER: Nakayama E 

PROVIDER: S-EPMC12024116 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature