Systemic expression of Kaposi sarcoma herpesvirus (KSHV) Vflip in endothelial cells leads to a profound proinflammatory phenotype and myeloid lineage remodeling in vivo. Academic Article uri icon

Overview

abstract

  • KSHV is the causative agent of Kaposi sarcoma (KS), a spindle-shaped endothelial cell neoplasm accompanied by an inflammatory infiltrate. To evaluate the role of KSHV vFLIP in the pathogenesis of KS, we constructed mice with inducible expression of vFLIP in endothelial cells. Abnormal cells with endothelial marker expression and fusiform appearance were observed in several tissues reminiscent of the spindle cells found in KS. Serum cytokines displayed a profound perturbation similar to that described in KSHV inflammatory cytokine syndrome (KICS), a recently described clinical condition characterized by elevated IL6 and IL10. An increased myeloid component with suppressive immune phenotype was found, which may contribute to functional changes in the microenvironment and cellular heterogeneity as observed in KS. These mice represent the first in vivo demonstration that vFLIP is capable of inducing vascular abnormalities and changes in host microenvironment with important implications for understanding the pathogenesis and treating KSHV-associated diseases.

publication date

  • January 21, 2015

Research

keywords

  • Endothelial Cells
  • Inflammation
  • Myeloid Cells
  • Viral Proteins

Identity

PubMed Central ID

  • PMC4301867

Scopus Document Identifier

  • 84923839967

Digital Object Identifier (DOI)

  • 10.1016/S0002-9440(10)64940-1

PubMed ID

  • 25607954

Additional Document Info

volume

  • 11

issue

  • 1