Hantaviral mechanisms driving HLA class I antigen presentation require both RIG-I and TRIF.

Abstract

Hantaviruses are emerging human pathogens. They induce an unusually strong antiviral response of human HLA class I (HLA-I) restricted CD8⁺ T cells that may contribute to tissue damage and hantavirus-associated disease. In this study, we analyzed possible hantaviral mechanisms that enhance the HLA-I antigen presentation machinery. Upon hantavirus infection of various human and primate cell lines, we observed transactivation of promoters controlling classical HLA molecules. Hantavirus-induced HLA-I upregulation required proteasomal activity and was associated with increased TAP expression. Intriguingly, human DCs acquired the capacity to cross-present antigen upon hantavirus infection. Furthermore, knockdown of TIR domain containing adaptor inducing IFN-β or retinoic acid inducible gene I abolished hantavirus-driven HLA-I induction. In contrast, MyD88-dependent viral sensors were not involved in HLA-I induction. Our results show that hantaviruses strongly boost the HLA-I antigen presentation machinery by mechanisms that are dependent on both retinoic acid inducible gene I and TIR domain containing adaptor inducing IFN-β.

• Authors: Pritesh Lalwani, Martin J Raftery, Lidija Kobak, Andreas Rang, Thomas Giese, Markus Matthaei, Peter J van den Elsen, Thorsten Wolff, Detlev H Krüger, Günther Schönrich
• Journal: European journal of immunology (Eur J Immunol) Vol. 43 Issue 10 Pg. 2566-76 (Oct 2013) ISSN: 1521-4141 [Electronic] Germany
• PMID: 23824566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• ATP-Binding Cassette Transporters
• Adaptor Proteins, Vesicular Transport
• HLA Antigens
• PLAAT4 protein, human
• RNA, Small Interfering
• Receptors, Retinoic Acid
• TICAM1 protein, human
• Proteasome Endopeptidase Complex

Topics

• ATP-Binding Cassette Transporters (metabolism)
• Adaptor Proteins, Vesicular Transport (genetics, metabolism)
• Animals
• Antigen Presentation
• Chlorocebus aethiops
• Cross-Priming (genetics)
• Dendritic Cells (immunology, virology)
• HLA Antigens (genetics, metabolism)
• Orthohantavirus (immunology)
• Hantavirus Infections (immunology)
• Humans
• Proteasome Endopeptidase Complex (metabolism)
• RNA, Small Interfering (genetics)
• Receptors, Retinoic Acid (genetics, metabolism)
• Up-Regulation
• Vero Cells