IRF-4-mediated CIITA transcription is blocked by KSHV encoded LANA to inhibit MHC II presentation

Qiliang Cai, Shuvomoy Banerjee, Amanda Cervini, Jie Lu, Andrew D Hislop, Richard Dzeng, Erle S Robertson

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Peptides presentation to T cells by MHC class II molecules is of importance in initiation of immune response to a pathogen. The level of MHC II expression directly influences T lymphocyte activation and is often targeted by various viruses. Kaposi's sarcoma-associated herpesvirus (KSHV) encoded LANA is known to evade MHC class I peptide processing, however, the effect of LANA on MHC class II remains unclear. Here, we report that LANA down-regulates MHC II expression and presentation by inhibiting the transcription of MHC II transactivator (CIITA) promoter pIII and pIV in a dose-dependent manner. Strikingly, although LANA knockdown efficiently disrupts the inhibition of CIITA transcripts from its pIII and pIV promoter region, the expression of HLA-DQβ but no other MHC II molecules was significantly restored. Moreover, we revealed that the presentation of HLA-DQβ enhanced by LANA knockdown did not help LANA-specific CD4+ T cell recognition of PEL cells, and the inhibition of CIITA by LANA is independent of IL-4 or IFN-γ signaling but dependent on the direct interaction of LANA with IRF-4 (an activator of both the pIII and pIV CIITA promoters). This interaction dramatically blocked the DNA-binding ability of IRF-4 on both pIII and pIV promoters. Thus, our data implies that LANA can evade MHC II presentation and suppress CIITA transcription to provide a unique strategy of KSHV escape from immune surveillance by cytotoxic T cells.

Original languageEnglish
Article numbere1003751
JournalPLoS pathogens
Issue number10
Publication statusPublished - 31 Oct 2013


  • Antigen Presentation
  • Antigens, Viral
  • Down-Regulation
  • Female
  • HEK293 Cells
  • HLA-DQ beta-Chains
  • Herpesvirus 8, Human
  • Humans
  • Interferon Regulatory Factors
  • Interferon-gamma
  • Interleukin-4
  • Male
  • Nuclear Proteins
  • Response Elements
  • Trans-Activators
  • Transcription, Genetic


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