The CXCL8/MAPK/hnRNP-K Axis Enables Susceptibility to Infection by EV-D68, Rhinovirus, and Influenza Virus in Vitro

Overview

Journal Nat Commun

Specialty Biology

Date 2025 Feb 17

PMID 39962077

Authors

Qingran Yang

Haoran Guo

Huili Li

Zhaoxue Li

Fushun Ni

Zhongmei Wen

Kai Liu

Huihui Kong

Wei Wei

Affiliations

Soon will be listed here.

Abstract

Respiratory viruses pose an ongoing threat to human health with excessive cytokine secretion contributing to severe illness and mortality. However, the relationship between cytokine secretion and viral infection remains poorly understood. Here we elucidate the role of CXCL8 as an early response gene to EV-D68 infection. Silencing CXCL8 or its receptors, CXCR1/2, impedes EV-D68 replication in vitro. Upon recognition of CXCL8 by CXCR1/2, the MAPK pathway is activated, facilitating the translocation of nuclear hnRNP-K to the cytoplasm. This translocation increases the recognition of viral RNA by hnRNP-K in the cytoplasm, promoting the function of the 5' untranslated region in the viral genome. Moreover, our investigations also reveal the importance of the CXCL8 signaling pathway in the replication of both influenza virus and rhinovirus. In summary, our findings hint that these viruses exploit the CXCL8/MAPK/hnRNP-K axis to enhance viral replication in respiratory cells in vitro.

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