The Experts below are selected from a list of 1371 Experts worldwide ranked by ideXlab platform
Hua Zhang - One of the best experts on this subject based on the ideXlab platform.
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bioactive aromatic butenolides from a mangrove sediment originated fungal species aspergillus terreus scau011
Fitoterapia, 2021Co-Authors: Jie Bao, Kongkai Zhu, Yinyin Wang, Xiaoyong Zhang, Hua ZhangAbstract:Abstract Seven new compounds including five aromatic butenolide analogues (1–5), one quinazolinone alkaloid (6) and one Benzoic Acid Derivative (7), along with eleven known co-metabolites (8–18), were isolated from Aspergillus terreus SCAU011, a fungus from the rhizosphere sediment of a mangrove plant Rhizophora stylosa. The structures of these isolates were established by a combination of MS, NMR and ECD data analyses, as well as chemical method. Compound 3 is a rare ring-open aromatic butenolide, while 6 represents the first natural ring-open benzomalvin-type quinazolinone alkaloid. Also, the previously reported structures for asperlides A–C were proposed to be revised in the present work. The COX-2 inhibitory, α-glucosidase inhibitory, antioxidant and antibacterial activities of all the compounds were assessed. While compounds 4, 6, 11 and 18 exhibited better COX-2 inhibitory activity than the positive control celecoxib, compounds 9 and 10 showed significant α-glucosidase inhibitory activity with IC50 values of 56.1 and 12.9 μM, respectively. Meanwhile, half of the tested samples (1, 8–11 and 15–17) exerted similar or better antioxidant activity compared with the reference drug curcumin, and compounds 3, 9, 17 and 18 displayed moderate antibacterial effect against Staphylococcus aureus.
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author correction ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Dan Xiong, Yan Min Liu, Ai Jun Zhou, Qian ZhongAbstract:In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl Benzoic Acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl Benzoic Acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl Benzoic Acid Derivative. All references to 2,5-dimethylpyrrolyl Benzoic Acid in the Letter have now been changed to reflect this. Although 2,5-dimethylpyrrolyl Benzoic Acid Derivatives have been reported to have off-target effects2, as do most small-molecule inhibitors, the multiple complementary methods and techniques used demonstrate that EphA2 is a key Epstein–Barr virus epithelial cell receptor. The conclusions of the study are therefore unchanged.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry. The receptor tyrosine kinase EphA2 is found to be an important determinant of EBV entry and fusion in epithelial cells. EphA2 depletion or absence, or the use of anti-EphA2 antibodies, inhibits oropharyngeal epithelial cell infection.
Dan Xiong - One of the best experts on this subject based on the ideXlab platform.
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author correction ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Dan Xiong, Yan Min Liu, Ai Jun Zhou, Qian ZhongAbstract:In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl Benzoic Acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl Benzoic Acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl Benzoic Acid Derivative. All references to 2,5-dimethylpyrrolyl Benzoic Acid in the Letter have now been changed to reflect this. Although 2,5-dimethylpyrrolyl Benzoic Acid Derivatives have been reported to have off-target effects2, as do most small-molecule inhibitors, the multiple complementary methods and techniques used demonstrate that EphA2 is a key Epstein–Barr virus epithelial cell receptor. The conclusions of the study are therefore unchanged.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry. The receptor tyrosine kinase EphA2 is found to be an important determinant of EBV entry and fusion in epithelial cells. EphA2 depletion or absence, or the use of anti-EphA2 antibodies, inhibits oropharyngeal epithelial cell infection.
Zhi Xin Fang - One of the best experts on this subject based on the ideXlab platform.
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author correction ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Dan Xiong, Yan Min Liu, Ai Jun Zhou, Qian ZhongAbstract:In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl Benzoic Acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl Benzoic Acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl Benzoic Acid Derivative. All references to 2,5-dimethylpyrrolyl Benzoic Acid in the Letter have now been changed to reflect this. Although 2,5-dimethylpyrrolyl Benzoic Acid Derivatives have been reported to have off-target effects2, as do most small-molecule inhibitors, the multiple complementary methods and techniques used demonstrate that EphA2 is a key Epstein–Barr virus epithelial cell receptor. The conclusions of the study are therefore unchanged.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry. The receptor tyrosine kinase EphA2 is found to be an important determinant of EBV entry and fusion in epithelial cells. EphA2 depletion or absence, or the use of anti-EphA2 antibodies, inhibits oropharyngeal epithelial cell infection.
Mei Ling Chen - One of the best experts on this subject based on the ideXlab platform.
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author correction ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Dan Xiong, Yan Min Liu, Ai Jun Zhou, Qian ZhongAbstract:In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl Benzoic Acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl Benzoic Acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl Benzoic Acid Derivative. All references to 2,5-dimethylpyrrolyl Benzoic Acid in the Letter have now been changed to reflect this. Although 2,5-dimethylpyrrolyl Benzoic Acid Derivatives have been reported to have off-target effects2, as do most small-molecule inhibitors, the multiple complementary methods and techniques used demonstrate that EphA2 is a key Epstein–Barr virus epithelial cell receptor. The conclusions of the study are therefore unchanged.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry. The receptor tyrosine kinase EphA2 is found to be an important determinant of EBV entry and fusion in epithelial cells. EphA2 depletion or absence, or the use of anti-EphA2 antibodies, inhibits oropharyngeal epithelial cell infection.
Ao Zhang - One of the best experts on this subject based on the ideXlab platform.
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author correction ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Dan Xiong, Yan Min Liu, Ai Jun Zhou, Qian ZhongAbstract:In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl Benzoic Acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl Benzoic Acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl Benzoic Acid Derivative. All references to 2,5-dimethylpyrrolyl Benzoic Acid in the Letter have now been changed to reflect this. Although 2,5-dimethylpyrrolyl Benzoic Acid Derivatives have been reported to have off-target effects2, as do most small-molecule inhibitors, the multiple complementary methods and techniques used demonstrate that EphA2 is a key Epstein–Barr virus epithelial cell receptor. The conclusions of the study are therefore unchanged.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry.
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ephrin receptor a2 is an epithelial cell receptor for epstein barr virus entry
Nature microbiology, 2018Co-Authors: Hua Zhang, Hong Bo Wang, Ao Zhang, Mei Ling Chen, Zhi Xin Fang, Xiao Dong Dong, Yan Li, Shi Bing Li, Yong Du, Dan XiongAbstract:Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR–Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl Benzoic Acid Derivative efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi’s sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry. The receptor tyrosine kinase EphA2 is found to be an important determinant of EBV entry and fusion in epithelial cells. EphA2 depletion or absence, or the use of anti-EphA2 antibodies, inhibits oropharyngeal epithelial cell infection.