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Inhibiting the Recruitment of PLCγ1 to Kaposi’s Sarcoma Herpesvirus K15 Protein Reduces the Invasiveness and Angiogenesis of Infected Endothelial Cells


Kaposi’s Sarcoma (KS), etiologically linked to Kaposi’s sarcoma herpesvirus (KSHV), is a tumour of endothelial origin characterised by angiogenesis and invasiveness. In vitro, KSHV infected endothelial cells display an increased invasiveness and high angiogenicity. Here we report that the KSHV protein K15, which increases the angiogenicity of endothelial cells, contributes to KSHV-mediated invasiveness by the recruitment and activation of the cellular protein PLCγ1 and its downstream effectors βPIX, GIT1 and cdc42. We explored the functional consequences of disrupting the K15-PLCγ1 interaction by using an isolated PLCγ2 cSH2 domain as a dominant negative inhibitor. This protein fragment, by interacting with K15, reduces K15-driven recruitment and activation of PLCγ1 in a dose-dependent manner. Moreover, the PCLγ2 cSH2 domain, when overexpressed in KSHV infected endothelial cells, reduces the angiogenesis and invasiveness induced by the virus. These findings highlight the role of the K15-PLCγ1 interaction in KSHV-mediated invasiveness and identify it as a possible therapeutic target.


Vyšlo v časopise: Inhibiting the Recruitment of PLCγ1 to Kaposi’s Sarcoma Herpesvirus K15 Protein Reduces the Invasiveness and Angiogenesis of Infected Endothelial Cells. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005105
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005105

Souhrn

Kaposi’s Sarcoma (KS), etiologically linked to Kaposi’s sarcoma herpesvirus (KSHV), is a tumour of endothelial origin characterised by angiogenesis and invasiveness. In vitro, KSHV infected endothelial cells display an increased invasiveness and high angiogenicity. Here we report that the KSHV protein K15, which increases the angiogenicity of endothelial cells, contributes to KSHV-mediated invasiveness by the recruitment and activation of the cellular protein PLCγ1 and its downstream effectors βPIX, GIT1 and cdc42. We explored the functional consequences of disrupting the K15-PLCγ1 interaction by using an isolated PLCγ2 cSH2 domain as a dominant negative inhibitor. This protein fragment, by interacting with K15, reduces K15-driven recruitment and activation of PLCγ1 in a dose-dependent manner. Moreover, the PCLγ2 cSH2 domain, when overexpressed in KSHV infected endothelial cells, reduces the angiogenesis and invasiveness induced by the virus. These findings highlight the role of the K15-PLCγ1 interaction in KSHV-mediated invasiveness and identify it as a possible therapeutic target.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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