An identical miRNA of the human JC and BK polyoma viruses targets the stress-induced ligand ULBP3 to escape immune elimination

Yoav Bauman, Daphna Nachmani, Alon Vitenshtein, Pinchas Tsukerman, Nir Drayman, Noam Stern-Ginossar, Dikla Lankry, Raizy Gruda, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

The human polyoma viruses JCV and BKV establish asymptomatic persistent infection in 65%-90% of humans but can cause severe illness under immunosuppressive conditions. The mechanisms by which these viruses evade immune recognition are unknown. Here we show that a viral miRNA identical in sequence between JCV and BKV targets the stress-induced ligand ULBP3, which is a protein recognized by the killer receptor NKG2D. Consequently, viral miRNA-mediated ULBP3 downregulation results in reduced NKG2D-mediated killing of virus-infected cells by natural killer (NK) cells. Importantly, when the activity of the viral miRNA was inhibited during infection, NK cells killed the infected cells more efficiently. Because NKG2D is also expressed by various T cell subsets, we propose that JCV and BKV use an identical miRNA that targets ULBP3 to escape detection by both the innate and adaptive immune systems, explaining how these viruses remain latent without being eliminated by the immune system.

Original languageAmerican English
Pages (from-to)93-102
Number of pages10
JournalCell Host and Microbe
Volume9
Issue number2
DOIs
StatePublished - 17 Feb 2011

Bibliographical note

Funding Information:
This study was supported by grants from the Israeli Science Foundation, The Israeli Science Foundation (Morasha), The Croatia Israel Research Grant, The MOST-DKFZ Research grant, and The European Consortium (MRTN-CT-2005); and by the Rosetrees trust, the Israel Cancer Association (20100003), the ICRF professorship grant, and the Association for International Cancer Research (AICR) (all to O.M.). O.M. is a Crown professor of Molecular Immunology. Y.B. performed all experiments, analyzed the data, and wrote the paper. D.N., A.V., P.T., N.D., N.S.-G., D.L., and R.G. all contributed critical help and reagents. O.M. supervised the project.

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