Flavivirus Concentrates Host ER in Main Replication Compartments to Facilitate Replication
Yali Ci 1 2, Kai Han 1 2, Jie Kong 1,
Shuhan Huang 1 2, Yang Yang 1 2, Cheng-Feng Qin 3, Lei Shi 1 2
Adv Sci (Weinh).2023 Oct 27:e2305093. doi:
10.1002/advs.202305093.
PMID: 37888856
Abstract
Flavivirus remodels the host endoplasmic
reticulum (ER) to generate replication compartments (RCs) as the fundamental
structures to accommodate viral replication. Here, a centralized replication
mode of flavivirus is reported, i.e., flavivirus concentrates host ER in
perinuclear main replication compartments (MRCs) for efficient replication.
Superresolution live-cell imaging demonstrated that flavivirus MRCs formed via
a series of events, including multisite ER clustering, growth and merging of ER
clusters, directional movement, and convergence in the perinuclear region. The
dynamic activities of viral RCs are driven by nonstructural (NS) proteins and
are independent of microtubules and actin. Moreover, disrupting MRCs formation
by small molecule compounds inhibited flavivirus replication. Overall, the
findings reveal unprecedented insight into dynamic ER reorganization by flavivirus
and identify a new inhibition strategy.