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. 2022 Mar 3;13:847588. doi: 10.3389/fmicb.2022.847588

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Copyright © 2022 Fishburn, Pham, Kenaston, Beesabathuni and Shah.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Flaviviruses co-opt host proteins to remodel the ER. Flaviviruses dramatically alter the morphology of the host ER to create a niche that maximizes the efficiency of genome replication and virion packaging. Replication compartments are formed by the involution of the ER membrane by both viral and host proteins. Viral replication complexes reside within these compartments and carry out RNA replication. These complexes also physically associate with host proteins. Viral single-stranded RNA (ssRNA)+ genomes are translated on the ER by host ribosomes. The resulting viral polyprotein is co-translationally processed to ensure its stability, insertion into the ER membrane, and proper cleavage into individual viral proteins. *TMEM41B is known to interact with either ZIKV NS4A or YFV NS4B and may facilitate ER remodeling.