The KSHV viral IL-6 homolog is sufficient to induce blood to lymphatic endothelial cell differentiation

详细信息	查看全文 | 推荐本文 |

• 作者：Valerie A. Morris^a ; Almira S. Punjabi^a ; Robert C. Wells^a ; Cristina J. Wittkopp^a ; Richard Vart^b ; Michael Lagunoff^a ; ^{lagunoff@u.washington.edu}
• 关键词：KSHV ; HHV-8 ; Kaposi's Sarcoma ; vIL-6 ; Lymphatic endothelial cells ; Lymphatic endothelial cell differentiation
• 刊名：Virology
• 出版年：2012
• 期刊代码：108_00426822
• 类别：imm
• 出版时间：5 July, 2012
• 卷：428
• 期：2
• 页码：112-120
• 文件大小：627 K

摘要

The predominant tumor cell of Kaposi's Sarcoma (KS) is the spindle cell, a cell of endothelial origin that expresses markers of lymphatic endothelium. In culture, Kaposi's Sarcoma-associated herpesvirus (KSHV) infection of blood endothelial cells drives expression of lymphatic endothelial cell specific markers, in a process that requires activation of the gp130 receptor and the JAK2/STAT3 and PI3K/AKT signaling pathways. While expression of each of the KSHV major latent genes in endothelial cells failed to increase expression of lymphatic markers, the viral homolog of human IL-6 (vIL-6) was sufficient for induction and requires the JAK2/STAT3 and PI3K/AKT pathways. Therefore, activation of gp130 and downstream signaling by vIL-6 is sufficient to drive blood to lymphatic endothelial cell differentiation. While sufficient, vIL-6 is not necessary for lymphatic reprogramming in the context of viral infection. This indicates that multiple viral genes are involved and suggests a central importance of this pathway to KSHV pathogenesis.