The Experts below are selected from a list of 4227 Experts worldwide ranked by ideXlab platform

Richard Longnecker - One of the best experts on this subject based on the ideXlab platform.

  • Ephrin Receptor A4 is a new kaposi s sarcoma associated herpesvirus virus entry Receptor
    Mbio, 2019
    Co-Authors: Jia Chen, Xianming Zhang, Samantha Schaller, Theodore S Jardetzky, Richard Longnecker
    Abstract:

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with the development of Kaposi's sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In the current studies, we have found that EphA4 promotes KSHV glycoprotein H/glycoprotein L (gH/gL)-mediated fusion and infection better than does Ephrin A2 (EphA2) in HEK293T cells, indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA sequencing (RNA-seq) data analysis of existing data sets. We found that these cell types broadly express both EphA2 and EphA4, with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single- and double-knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2-EphA4 double-knockout cells had the greatest decrease in fusion activity and infection compared to single-knockout cells. Fusion and infection of KSHV were rescued in the EphA2-EphA4 double-knockout cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both Epstein-Barr virus (EBV) and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV.IMPORTANCE The overall entry mechanism for herpesviruses is not completely known, including those for the human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In the current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV, whereas EphA2 does. The discovery of EphA4 as a KSHV entry Receptor has important implications for KSHV pathogenesis in humans, may prove useful in understanding the unique pathogenesis of KSHV infection in humans, and may uncover new potential targets that can be used for the development of novel interventional strategies.

  • Ephrin Receptor A4 ephA4 is a new kaposi s sarcoma associated herpesvirus virus entry Receptor
    bioRxiv, 2019
    Co-Authors: Jia Chen, Samantha Schaller, Theodore S Jardetzky, Zianming Zhang, Richard Longnecker
    Abstract:

    Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus associated with the development of Kaposi’s sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In our current studies, we have found that EphA4 promotes KSHV gH/gL-mediated fusion and infection better than EphA2 in HEK293T cells indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA-seq data analysis of existing data sets. We found these cell types broadly express both EphA2 and EphA4 with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single and double knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2/EphA4 double knockout cells had the greatest decrease in fusion activity and infection compared to single knockout cells. Fusion and infection of KSHV was rescued in the EphA2/EphA4 double knock cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both EBV and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV. Importance The overall entry mechanism for herpesviruses is not completely known including that for the human γ-herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In our current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV whereas EphA2 does. The discovery of EphA4 as KSHV entry Receptor has important implications for KSHV pathogenesis in humans and may prove useful in understanding the unique pathogenesis of KSHV infection in humans and may uncover new potential targets that can be used for the development of novel interventional strategies.

  • Ephrin Receptor A4 is a New Kaposi’s Sarcoma-Associated Herpesvirus Virus Entry Receptor
    American Society for Microbiology, 2019
    Co-Authors: Jia Chen, Xianming Zhang, Samantha Schaller, Theodore S Jardetzky, Richard Longnecker
    Abstract:

    The overall entry mechanism for herpesviruses is not completely known, including those for the human gammaherpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In the current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV, whereas EphA2 does. The discovery of EphA4 as a KSHV entry Receptor has important implications for KSHV pathogenesis in humans, may prove useful in understanding the unique pathogenesis of KSHV infection in humans, and may uncover new potential targets that can be used for the development of novel interventional strategies.Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with the development of Kaposi’s sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In the current studies, we have found that EphA4 promotes KSHV glycoprotein H/glycoprotein L (gH/gL)-mediated fusion and infection better than does Ephrin A2 (EphA2) in HEK293T cells, indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA sequencing (RNA-seq) data analysis of existing data sets. We found that these cell types broadly express both EphA2 and EphA4, with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single- and double-knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2-EphA4 double-knockout cells had the greatest decrease in fusion activity and infection compared to single-knockout cells. Fusion and infection of KSHV were rescued in the EphA2-EphA4 double-knockout cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both Epstein-Barr virus (EBV) and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV

Jia Chen - One of the best experts on this subject based on the ideXlab platform.

  • Ephrin Receptor A4 is a new kaposi s sarcoma associated herpesvirus virus entry Receptor
    Mbio, 2019
    Co-Authors: Jia Chen, Xianming Zhang, Samantha Schaller, Theodore S Jardetzky, Richard Longnecker
    Abstract:

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with the development of Kaposi's sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In the current studies, we have found that EphA4 promotes KSHV glycoprotein H/glycoprotein L (gH/gL)-mediated fusion and infection better than does Ephrin A2 (EphA2) in HEK293T cells, indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA sequencing (RNA-seq) data analysis of existing data sets. We found that these cell types broadly express both EphA2 and EphA4, with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single- and double-knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2-EphA4 double-knockout cells had the greatest decrease in fusion activity and infection compared to single-knockout cells. Fusion and infection of KSHV were rescued in the EphA2-EphA4 double-knockout cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both Epstein-Barr virus (EBV) and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV.IMPORTANCE The overall entry mechanism for herpesviruses is not completely known, including those for the human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In the current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV, whereas EphA2 does. The discovery of EphA4 as a KSHV entry Receptor has important implications for KSHV pathogenesis in humans, may prove useful in understanding the unique pathogenesis of KSHV infection in humans, and may uncover new potential targets that can be used for the development of novel interventional strategies.

  • Ephrin Receptor A4 ephA4 is a new kaposi s sarcoma associated herpesvirus virus entry Receptor
    bioRxiv, 2019
    Co-Authors: Jia Chen, Samantha Schaller, Theodore S Jardetzky, Zianming Zhang, Richard Longnecker
    Abstract:

    Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus associated with the development of Kaposi’s sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In our current studies, we have found that EphA4 promotes KSHV gH/gL-mediated fusion and infection better than EphA2 in HEK293T cells indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA-seq data analysis of existing data sets. We found these cell types broadly express both EphA2 and EphA4 with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single and double knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2/EphA4 double knockout cells had the greatest decrease in fusion activity and infection compared to single knockout cells. Fusion and infection of KSHV was rescued in the EphA2/EphA4 double knock cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both EBV and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV. Importance The overall entry mechanism for herpesviruses is not completely known including that for the human γ-herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In our current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV whereas EphA2 does. The discovery of EphA4 as KSHV entry Receptor has important implications for KSHV pathogenesis in humans and may prove useful in understanding the unique pathogenesis of KSHV infection in humans and may uncover new potential targets that can be used for the development of novel interventional strategies.

  • Ephrin Receptor A4 is a New Kaposi’s Sarcoma-Associated Herpesvirus Virus Entry Receptor
    American Society for Microbiology, 2019
    Co-Authors: Jia Chen, Xianming Zhang, Samantha Schaller, Theodore S Jardetzky, Richard Longnecker
    Abstract:

    The overall entry mechanism for herpesviruses is not completely known, including those for the human gammaherpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In the current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV, whereas EphA2 does. The discovery of EphA4 as a KSHV entry Receptor has important implications for KSHV pathogenesis in humans, may prove useful in understanding the unique pathogenesis of KSHV infection in humans, and may uncover new potential targets that can be used for the development of novel interventional strategies.Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with the development of Kaposi’s sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In the current studies, we have found that EphA4 promotes KSHV glycoprotein H/glycoprotein L (gH/gL)-mediated fusion and infection better than does Ephrin A2 (EphA2) in HEK293T cells, indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA sequencing (RNA-seq) data analysis of existing data sets. We found that these cell types broadly express both EphA2 and EphA4, with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single- and double-knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2-EphA4 double-knockout cells had the greatest decrease in fusion activity and infection compared to single-knockout cells. Fusion and infection of KSHV were rescued in the EphA2-EphA4 double-knockout cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both Epstein-Barr virus (EBV) and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV

Samantha Schaller - One of the best experts on this subject based on the ideXlab platform.

  • Ephrin Receptor A4 is a new kaposi s sarcoma associated herpesvirus virus entry Receptor
    Mbio, 2019
    Co-Authors: Jia Chen, Xianming Zhang, Samantha Schaller, Theodore S Jardetzky, Richard Longnecker
    Abstract:

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with the development of Kaposi's sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In the current studies, we have found that EphA4 promotes KSHV glycoprotein H/glycoprotein L (gH/gL)-mediated fusion and infection better than does Ephrin A2 (EphA2) in HEK293T cells, indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA sequencing (RNA-seq) data analysis of existing data sets. We found that these cell types broadly express both EphA2 and EphA4, with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single- and double-knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2-EphA4 double-knockout cells had the greatest decrease in fusion activity and infection compared to single-knockout cells. Fusion and infection of KSHV were rescued in the EphA2-EphA4 double-knockout cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both Epstein-Barr virus (EBV) and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV.IMPORTANCE The overall entry mechanism for herpesviruses is not completely known, including those for the human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In the current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV, whereas EphA2 does. The discovery of EphA4 as a KSHV entry Receptor has important implications for KSHV pathogenesis in humans, may prove useful in understanding the unique pathogenesis of KSHV infection in humans, and may uncover new potential targets that can be used for the development of novel interventional strategies.

  • Ephrin Receptor A4 ephA4 is a new kaposi s sarcoma associated herpesvirus virus entry Receptor
    bioRxiv, 2019
    Co-Authors: Jia Chen, Samantha Schaller, Theodore S Jardetzky, Zianming Zhang, Richard Longnecker
    Abstract:

    Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus associated with the development of Kaposi’s sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In our current studies, we have found that EphA4 promotes KSHV gH/gL-mediated fusion and infection better than EphA2 in HEK293T cells indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA-seq data analysis of existing data sets. We found these cell types broadly express both EphA2 and EphA4 with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single and double knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2/EphA4 double knockout cells had the greatest decrease in fusion activity and infection compared to single knockout cells. Fusion and infection of KSHV was rescued in the EphA2/EphA4 double knock cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both EBV and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV. Importance The overall entry mechanism for herpesviruses is not completely known including that for the human γ-herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In our current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV whereas EphA2 does. The discovery of EphA4 as KSHV entry Receptor has important implications for KSHV pathogenesis in humans and may prove useful in understanding the unique pathogenesis of KSHV infection in humans and may uncover new potential targets that can be used for the development of novel interventional strategies.

  • Ephrin Receptor A4 is a New Kaposi’s Sarcoma-Associated Herpesvirus Virus Entry Receptor
    American Society for Microbiology, 2019
    Co-Authors: Jia Chen, Xianming Zhang, Samantha Schaller, Theodore S Jardetzky, Richard Longnecker
    Abstract:

    The overall entry mechanism for herpesviruses is not completely known, including those for the human gammaherpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In the current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV, whereas EphA2 does. The discovery of EphA4 as a KSHV entry Receptor has important implications for KSHV pathogenesis in humans, may prove useful in understanding the unique pathogenesis of KSHV infection in humans, and may uncover new potential targets that can be used for the development of novel interventional strategies.Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with the development of Kaposi’s sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In the current studies, we have found that EphA4 promotes KSHV glycoprotein H/glycoprotein L (gH/gL)-mediated fusion and infection better than does Ephrin A2 (EphA2) in HEK293T cells, indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA sequencing (RNA-seq) data analysis of existing data sets. We found that these cell types broadly express both EphA2 and EphA4, with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single- and double-knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2-EphA4 double-knockout cells had the greatest decrease in fusion activity and infection compared to single-knockout cells. Fusion and infection of KSHV were rescued in the EphA2-EphA4 double-knockout cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both Epstein-Barr virus (EBV) and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV

Theodore S Jardetzky - One of the best experts on this subject based on the ideXlab platform.

  • Ephrin Receptor A4 is a new kaposi s sarcoma associated herpesvirus virus entry Receptor
    Mbio, 2019
    Co-Authors: Jia Chen, Xianming Zhang, Samantha Schaller, Theodore S Jardetzky, Richard Longnecker
    Abstract:

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with the development of Kaposi's sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In the current studies, we have found that EphA4 promotes KSHV glycoprotein H/glycoprotein L (gH/gL)-mediated fusion and infection better than does Ephrin A2 (EphA2) in HEK293T cells, indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA sequencing (RNA-seq) data analysis of existing data sets. We found that these cell types broadly express both EphA2 and EphA4, with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single- and double-knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2-EphA4 double-knockout cells had the greatest decrease in fusion activity and infection compared to single-knockout cells. Fusion and infection of KSHV were rescued in the EphA2-EphA4 double-knockout cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both Epstein-Barr virus (EBV) and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV.IMPORTANCE The overall entry mechanism for herpesviruses is not completely known, including those for the human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In the current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV, whereas EphA2 does. The discovery of EphA4 as a KSHV entry Receptor has important implications for KSHV pathogenesis in humans, may prove useful in understanding the unique pathogenesis of KSHV infection in humans, and may uncover new potential targets that can be used for the development of novel interventional strategies.

  • Ephrin Receptor A4 ephA4 is a new kaposi s sarcoma associated herpesvirus virus entry Receptor
    bioRxiv, 2019
    Co-Authors: Jia Chen, Samantha Schaller, Theodore S Jardetzky, Zianming Zhang, Richard Longnecker
    Abstract:

    Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus associated with the development of Kaposi’s sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In our current studies, we have found that EphA4 promotes KSHV gH/gL-mediated fusion and infection better than EphA2 in HEK293T cells indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA-seq data analysis of existing data sets. We found these cell types broadly express both EphA2 and EphA4 with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single and double knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2/EphA4 double knockout cells had the greatest decrease in fusion activity and infection compared to single knockout cells. Fusion and infection of KSHV was rescued in the EphA2/EphA4 double knock cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both EBV and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV. Importance The overall entry mechanism for herpesviruses is not completely known including that for the human γ-herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In our current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV whereas EphA2 does. The discovery of EphA4 as KSHV entry Receptor has important implications for KSHV pathogenesis in humans and may prove useful in understanding the unique pathogenesis of KSHV infection in humans and may uncover new potential targets that can be used for the development of novel interventional strategies.

  • Ephrin Receptor A4 is a New Kaposi’s Sarcoma-Associated Herpesvirus Virus Entry Receptor
    American Society for Microbiology, 2019
    Co-Authors: Jia Chen, Xianming Zhang, Samantha Schaller, Theodore S Jardetzky, Richard Longnecker
    Abstract:

    The overall entry mechanism for herpesviruses is not completely known, including those for the human gammaherpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional Receptors need to be identified. In the current study, we found that EphA4 can also function for a KSHV entry Receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry Receptor for EBV, whereas EphA2 does. The discovery of EphA4 as a KSHV entry Receptor has important implications for KSHV pathogenesis in humans, may prove useful in understanding the unique pathogenesis of KSHV infection in humans, and may uncover new potential targets that can be used for the development of novel interventional strategies.Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with the development of Kaposi’s sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular Receptors. In the current studies, we have found that EphA4 promotes KSHV glycoprotein H/glycoprotein L (gH/gL)-mediated fusion and infection better than does Ephrin A2 (EphA2) in HEK293T cells, indicating that EphA4 is a new KSHV entry Receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA sequencing (RNA-seq) data analysis of existing data sets. We found that these cell types broadly express both EphA2 and EphA4, with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single- and double-knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2-EphA4 double-knockout cells had the greatest decrease in fusion activity and infection compared to single-knockout cells. Fusion and infection of KSHV were rescued in the EphA2-EphA4 double-knockout cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both Epstein-Barr virus (EBV) and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry Receptor for KSHV

Peter Weber - One of the best experts on this subject based on the ideXlab platform.

  • Identification and characterization of Nanobodies targeting the EphA4 Receptor
    The Journal of biological chemistry, 2017
    Co-Authors: Lies Schoonaert, Laura Rué, Bart Roucourt, Mieke Timmers, Susan J. Little, Lucía Chávez-gutiérrez, Maarten Dewilde, Peter Joyce, Adam Curnock, Peter Weber
    Abstract:

    The Ephrin Receptor A4 (EphA4) is one of the Receptors in the Ephrin system that plays a pivotal role in a variety of cell-cell interactions, mostly studied during development. In addition, EphA4 has been found to play a role in cancer biology as well as in the pathogenesis of several neurological disorders such as stroke, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease. Pharmacological blocking of EphA4 has been suggested to be a therapeutic strategy for these disorders. Therefore, the aim of our study was to generate potent and selective Nanobodies against the ligand-binding domain of the human EphA4 Receptor. We identified two Nanobodies, Nb 39 and Nb 53, that bind EphA4 with affinities in the nanomolar range. These Nanobodies were most selective for EphA4, with residual binding to EphA7 only. Using Alphascreen technology, we found that both Nanobodies displaced all known EphA4-binding Ephrins from the Receptor. Furthermore, Nb 39 and Nb 53 inhibited Ephrin-induced phosphorylation of the EphA4 protein in a cell-based assay. Finally, in a cortical neuron primary culture, both Nanobodies were able to inhibit endogenous EphA4-mediated growth-cone collapse induced by Ephrin-B3. Our results demonstrate the potential of Nanobodies to target the ligand-binding domain of EphA4. These Nanobodies may deserve further evaluation as potential therapeutics in disorders in which EphA4-mediated signaling plays a role.