Vesicle-associated membrane protein 5 is an intrinsic defense factor for embryonic stem cells against coronaviruses

Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomo...

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Published inNature communications Vol. 16; no. 1; pp. 6241 - 20
Main Authors Dong, Huijun, Pan, Zihang, Jiao, Pengtao, Ye, Fei, Peng, Qi, Yu, Yanying, Lai, Xinyuan, Li, Huan, Guan, Zhao, Deng, Juan, Shen, Tao, Tan, Wenjie, Shi, Yi, Ding, Qiang, Luo, Jianyuan, Li, Tong, Zhuang, Hui, Xiang, Kuanhui
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 07.07.2025
Nature Publishing Group
Nature Portfolio
Subjects
13/1
13/100
13/31
13/89
14/19
14/28
631/250/2499
631/326/596/4130
631/532/2117
64/60
Animals
Coronaviridae
Coronavirus - physiology
Coronaviruses
COVID-19
COVID-19 - virology
Embryo cells
Embryonic Stem Cells - immunology
Embryonic Stem Cells - metabolism
Embryonic Stem Cells - virology
HEK293 Cells
Humanities and Social Sciences
Humans
Interferon
Kinases
Membranes
Mesoderm
Mice
multidisciplinary
Proteins
R-SNARE Proteins - genetics
R-SNARE Proteins - metabolism
Replication
Ribonucleic acid
RNA
RNA, Viral
SARS-CoV-2 - genetics
SARS-CoV-2 - physiology
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Stem cells
Transcription
Viral diseases
Viral infections
Virus Replication
Viruses
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Abstract Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments. Stem cells are highly resistant to viral infection, irrespective of any interferon response. Here the authors discover that VAMP5 as a potent cell-autonomous defense factor protects ESCs from various viruses’ infection, including SARS-CoV-2 by interacting with RNA replication complexes to defend against viral infection.
AbstractList Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments. Stem cells are highly resistant to viral infection, irrespective of any interferon response. Here the authors discover that VAMP5 as a potent cell-autonomous defense factor protects ESCs from various viruses’ infection, including SARS-CoV-2 by interacting with RNA replication complexes to defend against viral infection.
Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments.Stem cells are highly resistant to viral infection, irrespective of any interferon response. Here the authors discover that VAMP5 as a potent cell-autonomous defense factor protects ESCs from various viruses’ infection, including SARS-CoV-2 by interacting with RNA replication complexes to defend against viral infection.
Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments.Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments.
Abstract Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments.
Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments.
ArticleNumber 6241
Author Shen, Tao
Shi, Yi
Xiang, Kuanhui
Tan, Wenjie
Li, Tong
Ding, Qiang
Deng, Juan
Pan, Zihang
Li, Huan
Guan, Zhao
Yu, Yanying
Luo, Jianyuan
Peng, Qi
Zhuang, Hui
Dong, Huijun
Ye, Fei
Lai, Xinyuan
Jiao, Pengtao
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Snippet Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying...
Abstract Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the...
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Animals
Coronaviridae
Coronavirus - physiology
Coronaviruses
COVID-19
COVID-19 - virology
Embryo cells
Embryonic Stem Cells - immunology
Embryonic Stem Cells - metabolism
Embryonic Stem Cells - virology
HEK293 Cells
Humanities and Social Sciences
Humans
Interferon
Kinases
Membranes
Mesoderm
Mice
multidisciplinary
Proteins
R-SNARE Proteins - genetics
R-SNARE Proteins - metabolism
Replication
Ribonucleic acid
RNA
RNA, Viral
SARS-CoV-2 - genetics
SARS-CoV-2 - physiology
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Stem cells
Transcription
Viral diseases
Viral infections
Virus Replication
Viruses
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Title Vesicle-associated membrane protein 5 is an intrinsic defense factor for embryonic stem cells against coronaviruses
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