XPO1 coordinates human cytomegalovirus maturation by modulating genome encapsidation and secondary envelopment.
4 affiliations
- 1State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China.
- 2University of Chinese Academy of Sciences, Beijing, 101408, China.
- 3State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China.
- 4Shanghai Public Health Clinical Center, Fudan University, Shanghai, 2000083, China.
Abstract
Human cytomegalovirus (HCMV) replication depends on tightly coordinated nuclear capsid assembly and cytoplasmic nucleocapsid maturation, yet host factors controlling these processes remain poorly defined. Here, we identify exportin 1 (XPO1) as a dual-phase regulator that coordinates HCMV maturation from nucleus to cytoplasm. XPO1 inhibition induces aberrant nuclear electron-dense speckles and accumulation of B-capsids. Mechanistically, nuclear retention of pp65 drives speckle formation but does not account for B-capsid accumulation. XPO1 recognizes a functional nuclear export signal (NES) within pUL77 and regulates its proper intranuclear localization. Inhibiting XPO1 or disrupting the NES induces intranuclear pUL77 aggregation and B-capsid accumulation. XPO1 is also required for viral assembly compartment formation and maintenance of late-stage autophagic flux, both of which are essential for secondary envelopment. Our findings highlight the key role of XPO1 in virion maturation and the therapeutic potential of repurposing FDA-approved XPO1 inhibitors as a host-directed antiviral strategy.
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BibTeX
@article{wu2026xpo1,
title = {{XPO1 coordinates human cytomegalovirus maturation by modulating genome encapsidation and secondary envelopment.}},
author = {Jin-Peng Wu and Yue-Peng Zhou and Meng-Jie Mei and Yu-Ting Pan and Jin-Yan Sun and Wen-Bo Zeng and Han Cheng and Min-Hua Luo and Bo Yang},
journal = {Cell insight},
year = {2026},
month = sep,
doi = {10.1016/j.cellin.2026.100364},
url = {https://europepmc.org/article/MED/42903897},
note = {CC BY},
}
RIS
TY - JOUR
TI - XPO1 coordinates human cytomegalovirus maturation by modulating genome encapsidation and secondary envelopment.
AU - Jin-Peng Wu
AU - Yue-Peng Zhou
AU - Meng-Jie Mei
AU - Yu-Ting Pan
AU - Jin-Yan Sun
AU - Wen-Bo Zeng
AU - Han Cheng
AU - Min-Hua Luo
AU - Bo Yang
PY - 2026
DA - 2026/09/09
JO - Cell insight
DO - 10.1016/j.cellin.2026.100364
UR - https://europepmc.org/article/MED/42903897
AB - Human cytomegalovirus (HCMV) replication depends on tightly coordinated nuclear capsid assembly and cytoplasmic nucleocapsid maturation, yet host factors controlling these processes remain poorly defined. Here, we identify exportin 1 (XPO1) as a dual-phase regulator that coordinates HCMV maturation from nucleus to cytoplasm. XPO1 inhibition induces aberrant nuclear electron-dense speckles and accumulation of B-capsids. Mechanistically, nuclear retention of pp65 drives speckle formation but does not account for B-capsid accumulation. XPO1 recognizes a functional nuclear export signal (NES) within pUL77 and regulates its proper intranuclear localization. Inhibiting XPO1 or disrupting the NES induces intranuclear pUL77 aggregation and B-capsid accumulation. XPO1 is also required for viral assembly compartment formation and maintenance of late-stage autophagic flux, both of which are essential for secondary envelopment. Our findings highlight the key role of XPO1 in virion maturation and the therapeutic potential of repurposing FDA-approved XPO1 inhibitors as a host-directed antiviral strategy.
SN - 2772-8927
ER -