Downregulation of IRF4 induces lytic reactivation of KSHV in primary effusion lymphoma cells

Virology. 2014 Jun:458-459:4-10. doi: 10.1016/j.virol.2014.04.020. Epub 2014 May 5.

Abstract

Primary effusion lymphoma (PEL), associated with the latent infection by KSHV, constitutively expresses interferon-regulatory factor 4 (IRF4). We recently showed that IRF4 differentially regulates expression of cellular interferon-stimulated genes (ISGs) and viral genes (Forero et al., 2013). Here, using inducible IRF4 knockdown, we demonstrate that IRF4 silencing results in enhanced transcription of KSHV replication transactivator RTA. As a result viral transcription is increased leading to virus reactivation. Taken together, our results show that IRF4 helps maintain the balance between latency and KSHV reactivation in PEL cells.

Keywords: Interferon regulatory factor 4; Kaposi׳s sarcoma-associated herpesvirus; Primary effusion lymphoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Down-Regulation
  • Gene Silencing
  • Herpesvirus 8, Human / physiology*
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism*
  • Virus Latency / physiology*

Substances

  • Interferon Regulatory Factors
  • interferon regulatory factor-4