MEK1/2 inhibition prevents DENV and ZIKV infection via disrupting the cytoskeletal vimentin cage required for viral replication.

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Main Authors: Huang, Yuhan, Lu, Jiageng, Cui, Shuzhi, Zhao, Shuangshuang, Sun, Shengming, Jiu, Yaming
Format: Artículo científico
Language:en
Published: Journal of molecular cell biology 2026
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author Huang, Yuhan
Lu, Jiageng
Cui, Shuzhi
Zhao, Shuangshuang
Sun, Shengming
Jiu, Yaming
author_facet Huang, Yuhan
Lu, Jiageng
Cui, Shuzhi
Zhao, Shuangshuang
Sun, Shengming
Jiu, Yaming
Huang, Yuhan
Lu, Jiageng
Cui, Shuzhi
Zhao, Shuangshuang
Sun, Shengming
Jiu, Yaming
collection PubMed - marine biology
contents MEK1/2 inhibition prevents DENV and ZIKV infection via disrupting the cytoskeletal vimentin cage required for viral replication. Huang, Yuhan Lu, Jiageng Cui, Shuzhi Zhao, Shuangshuang Sun, Shengming Jiu, Yaming Virus Replication Vimentin Humans Dengue Virus MAP Kinase Kinase 1 MAP Kinase Kinase 2 Zika Virus Zika Virus Infection Dengue Animals Cytoskeleton Protein Kinase Inhibitors Chlorocebus aethiops MAP Kinase Signaling System Vero Cells Flaviviridae Dengue virus (DENV) and Zika virus (ZIKV) have posed significant threats to global public health in the past decades. Despite extensive study on therapeutic strategies against these viruses, effective treatment options are still lacking. Within host cells, the cytoskeletal vimentin intermediate filament network facilitates viral replication during DENV and ZIKV infection by shrinking and forming a cage-like structure. Our previous work indicated that MEK1/2 inhibitors can induce the dispersion of vimentin, but their potential impact on flavivirus infection remains unclear. Here, we observed that the MEK1/2 signaling pathway is activated in host cells infected with DENV and ZIKV. Treatment with MEK1/2 inhibitors significantly impaired the replication of both viruses. Further mechanistic studies revealed that MEK1/2 inhibitors prevent viral infection by promoting the dispersion of intracellular vimentin network, thereby disrupting the cytoskeletal structure required for viral replication. Our findings not only expand the understanding of vimentin regulatory mechanisms from a cellular biology perspective but also provide a new perspective on MEK1/2 inhibition as a potential anti-DENV and anti-ZIKV strategy.
format Artículo científico
id pubmed_41137718
institution PubMed
language en
publishDate 2026
publisher Journal of molecular cell biology
record_format pubmed
spellingShingle MEK1/2 inhibition prevents DENV and ZIKV infection via disrupting the cytoskeletal vimentin cage required for viral replication.
Huang, Yuhan
Lu, Jiageng
Cui, Shuzhi
Zhao, Shuangshuang
Sun, Shengming
Jiu, Yaming
Virus Replication
Vimentin
Humans
Dengue Virus
MAP Kinase Kinase 1
MAP Kinase Kinase 2
Zika Virus
Zika Virus Infection
Dengue
Animals
Cytoskeleton
Protein Kinase Inhibitors
Chlorocebus aethiops
MAP Kinase Signaling System
Vero Cells
MEK1/2 inhibition prevents DENV and ZIKV infection via disrupting the cytoskeletal vimentin cage required for viral replication. Huang, Yuhan Lu, Jiageng Cui, Shuzhi Zhao, Shuangshuang Sun, Shengming Jiu, Yaming Virus Replication Vimentin Humans Dengue Virus MAP Kinase Kinase 1 MAP Kinase Kinase 2 Zika Virus Zika Virus Infection Dengue Animals Cytoskeleton Protein Kinase Inhibitors Chlorocebus aethiops MAP Kinase Signaling System Vero Cells Flaviviridae Dengue virus (DENV) and Zika virus (ZIKV) have posed significant threats to global public health in the past decades. Despite extensive study on therapeutic strategies against these viruses, effective treatment options are still lacking. Within host cells, the cytoskeletal vimentin intermediate filament network facilitates viral replication during DENV and ZIKV infection by shrinking and forming a cage-like structure. Our previous work indicated that MEK1/2 inhibitors can induce the dispersion of vimentin, but their potential impact on flavivirus infection remains unclear. Here, we observed that the MEK1/2 signaling pathway is activated in host cells infected with DENV and ZIKV. Treatment with MEK1/2 inhibitors significantly impaired the replication of both viruses. Further mechanistic studies revealed that MEK1/2 inhibitors prevent viral infection by promoting the dispersion of intracellular vimentin network, thereby disrupting the cytoskeletal structure required for viral replication. Our findings not only expand the understanding of vimentin regulatory mechanisms from a cellular biology perspective but also provide a new perspective on MEK1/2 inhibition as a potential anti-DENV and anti-ZIKV strategy.
title MEK1/2 inhibition prevents DENV and ZIKV infection via disrupting the cytoskeletal vimentin cage required for viral replication.
topic Virus Replication
Vimentin
Humans
Dengue Virus
MAP Kinase Kinase 1
MAP Kinase Kinase 2
Zika Virus
Zika Virus Infection
Dengue
Animals
Cytoskeleton
Protein Kinase Inhibitors
Chlorocebus aethiops
MAP Kinase Signaling System
Vero Cells
url https://pubmed.ncbi.nlm.nih.gov/41137718/