Kaposi’s Sarcoma-Associated Herpesvirus-Encoded Viral IL-6 (vIL-6) Enhances Immunoglobulin Class-Switch Recombination

Santas A. Rosario, Gabriel E. Santiago, Enrique A. Mesri, Ramiro E. Verdun

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic gamma-herpesvirus that causes AIDS-associated Kaposi sarcoma (KS) and several lymphoproliferative disorders. During the humoral immune response antigen-activated mature B cells acquire functional diversification by immunoglobulin heavy chain (IgH) class-switch recombination (CSR). CSR is initiated by activation-induced cytidine deaminase (AID) which targets highly repetitive switch (S)-regions to mediate DNA double-stranded breaks (DSBs) in the IgH locus facilitating intramolecular recombination. Here we show that in the context of cytokine stimulation, CSR is enhanced in murine B cells exposed only to replication-competent KSHV in an environment of KSHV infection, which coincided with elevated AID transcripts. Using murine splenic B cells and the mouse lymphoma CH12F3-2 CSR system, we identified that vIL-6, but not murine IL-6, increased class-switching, which correlated with upregulated AID expression. Together, these data suggest a regulatory role for KSHV vIL-6 in functionally modulating B cell biology by promoting CSR, which may in part explain how KSHV infection influences humoral immunity and affect KSHV pathogenesis.

Original languageEnglish (US)
Article number3119
JournalFrontiers in Microbiology
Volume9
DOIs
StatePublished - Mar 29 2018

Keywords

  • activation-induced cytidine deaminase
  • adaptive immunity
  • class-switch recombination
  • classical non-homologous end joining
  • heavy chain constant region
  • Kaposi’s sarcoma-associated herpesvirus
  • microhomology
  • viral IL-6

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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