Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 213, Issue 10, Pages 2065-2080Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20160248
Keywords
-
Categories
Funding
- Deutsche Forschungsgemeinschaft [SFB1054/TP B05 TP A03, SFB1064/TP A13, SFB-TR36/TP A04]
- Deutsche Krebshilfe [107277, 109661]
- National Institutes of Health [R01: CA70723, P01: CA022443]
- Deutscher Akademischer Austauschdienst
- European Molecular Biology Organization
Ask authors/readers for more resources
Epstein-Barr virus (EBV) is a tumor virus that establishes lifelong infection in most of humanity, despite eliciting strong and stable virus-specific immune responses. EBV encodes at least 44 miRNAs, most of them with unknown function. Here, we show that multiple EBV miRNAs modulate immune recognition of recently infected primary B cells, EBV's natural target cells. EBV miRNAs collectively and specifically suppress release of proinflammatory cytokines such as IL-12, repress differentiation of naive CD4(+) T cells to Th1 cells, interfere with peptide processing and presentation on HLA class II, and thus reduce activation of cytotoxic EBV-specific CD4(+) effector T cells and killing of infected B cells. Our findings identify a previously unknown viral strategy of immune evasion. By rapidly expressing multiple miRNAs, which are themselves nonimmunogenic, EBV counteracts recognition by CD4(+) T cells and establishes a program of reduced immunogenicity in recently infected B cells, allowing the virus to express viral proteins required for establishment of life-long infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available