Replication is the Key Barrier During the Dual-host Adaptation of Mosquito-borne Flaviviruses

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Mar 16

PMID 35294288

Authors

Yanan Zhang

Dening Liang

Fei Yuan

Yiran Yan

Zuoshu Wang

Pan Liu

Qi Yu

Xing Zhang

Xiangxi Wang

Aihua Zheng

Affiliations

Soon will be listed here.

Abstract

Mosquito-borne flaviviruses (MBFs) adapt to a dual-host transmission circle between mosquitoes and vertebrates. Dual-host affiliated insect-specific flaviviruses (dISFs), discovered from mosquitoes, are phylogenetically similar to MBFs but do not infect vertebrates. Thus, dISF–MBF chimeras could be an ideal model to study the dual-host adaptation of MBFs. Using the pseudoinfectious reporter virus particle and reverse genetics systems, we found dISFs entered vertebrate cells as efficiently as the MBFs but failed to initiate replication. Exchange of the untranslational regions (UTRs) of Donggang virus (DONV), a dISF, with those from Zika virus (ZIKV) rescued DONV replication in vertebrate cells, and critical secondary RNA structures were further mapped. Essential UTR-binding host factors were screened for ZIKV replication in vertebrate cells, displaying different binding patterns. Therefore, our data demonstrate a post-entry cross-species transmission mechanism of MBFs, while UTR-host interaction is critical for dual-host adaptation.

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