Activation of CD21 and CD23 gene expression by Kaposi's sarcoma-associated herpesvirus RTA. Academic Article uri icon

Overview

abstract

  • Epstein-Barr virus (EBV) EBNA2 and Kaposi's sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) are recruited to their responsive elements through interaction with a Notch-mediated transcription factor, RBP-Jkappa. In particular, RTA and EBNA2 interactions with RBP-Jkappa are essential for the lytic replication of KSHV and expression of B-cell activation markers CD21 and CD23a, respectively. Here, we demonstrate that like EBV EBNA2, KSHV RTA strongly induces CD21 and CD23a expression through RBP-Jkappa binding sites in the first intron of CD21 and in the CD23a core promoter, respectively. However, unlike EBV EBNA2, which alters immunoglobulin mu (Igmu) and c-myc gene expression, RTA did not affect Igmu and c-myc expression, indicating that KSHV RTA targets the Notch signal transduction pathway in a manner similar to but distinct from that of EBV EBNA2. Furthermore, RTA-induced expression of CD21 glycoprotein, which is an EBV receptor, efficiently facilitated EBV infection. In addition, RTA-induced CD23 glycoprotein underwent proteolysis and gave rise to soluble CD23 (sCD23) molecules in B lymphocytes and KSHV-infected primary effusion lymphocytes. sCD23 then stimulated primary human lymphocytes. These results demonstrate that cellular CD21 and CD23a are common targets for B lymphotropic gammaherpesviruses and that KSHV RTA regulates RBP-Jkappa-mediated cellular gene expression, which ultimately provides a favorable milieu for viral reproduction in the infected host.

publication date

  • April 1, 2005

Research

keywords

  • Herpesvirus 8, Human
  • Immediate-Early Proteins
  • Receptors, Complement 3d
  • Receptors, IgE
  • Trans-Activators
  • Viral Proteins

Identity

PubMed Central ID

  • PMC1069543

Scopus Document Identifier

  • 16244397745

Digital Object Identifier (DOI)

  • 10.1128/JVI.79.8.4651-4663.2005

PubMed ID

  • 15795251

Additional Document Info

volume

  • 79

issue

  • 8