EphA2 is a functional entry receptor for HCMV infection of glioblastoma cells

Human cytomegalovirus (HCMV) infection is associated with human glioblastoma, the most common and aggressive primary brain tumor, but the underlying infection mechanism has not been fully demonstrated. Here, we show that EphA2 was upregulated in glioblastoma and correlated with the poor prognosis of...

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Bibliographic Details
Published in:PLoS pathogens 2023-05, Vol.19 (5), p.e1011304-e1011304
Main Authors: Dong, Xiao-Dong, Li, Yan, Li, Ying, Sun, Cong, Liu, Shang-Xin, Duan, Hao, Cui, Run, Zhong, Qian, Mou, Yong-Gao, Wen, Le, Yang, Bo, Zeng, Mu-Sheng, Luo, Min-Hua, Zhang, Hua
Format: Article
Language:English
Subjects:
Antibodies
Biology and life sciences
Brain cancer
Brain tumors
Care and treatment
Cell cycle
Complications and side effects
Cytomegalovirus
Cytomegalovirus - physiology
Cytomegalovirus Infections
Development and progression
Efficiency
EphA2 protein
Ephrins
Experiments
Flow cytometry
Glioblastoma
Glioblastoma - genetics
Glioblastoma cells
Glioblastoma multiforme
Glycoproteins
Health aspects
Humans
Infection
Infections
Inhibitors
Kinases
Medical prognosis
Medicine and Health Sciences
Membrane fusion
Organoids
Prognosis
Protein expression
Proteins
Receptor, EphA2 - genetics
Research and Analysis Methods
Risk factors
Scientific equipment and supplies industry
Viral antibodies
Viral Envelope Proteins - metabolism
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Description
Summary:Human cytomegalovirus (HCMV) infection is associated with human glioblastoma, the most common and aggressive primary brain tumor, but the underlying infection mechanism has not been fully demonstrated. Here, we show that EphA2 was upregulated in glioblastoma and correlated with the poor prognosis of the patients. EphA2 silencing inhibits, whereas overexpression promotes HCMV infection, establishing EphA2 as a crucial cell factor for HCMV infection of glioblastoma cells. Mechanistically, EphA2 binds to HCMV gH/gL complex to mediate membrane fusion. Importantly, the HCMV infection was inhibited by the treatment of inhibitor or antibody targeting EphA2 in glioblastoma cells. Furthermore, HCMV infection was also impaired in optimal glioblastoma organoids by EphA2 inhibitor. Taken together, we propose EphA2 as a crucial cell factor for HCMV infection in glioblastoma cells and a potential target for intervention.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1011304