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Modulation of NKp30- and NKp46-mediated natural killer cell responses by poxviral hemagglutinin

Natural killer (NK) cells are an important element in the immune defense against the orthopox family members vaccinia virus (VV) and ectromelia virus (ECTV). NK cells are regulated through inhibitory and activating signaling receptors, the latter involving NKG2D and the natural cytotoxicity receptor...

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Main Authors: Jarahian, Mostafa (Author) , Fiedler, Manuela (Author) , Cohnen, André (Author) , Djandji, Dominik (Author) , Hämmerling, Günter J. (Author) , Gati, Cornelius (Author) , Cerwenka, Adelheid (Author) , Turner, Peter C. (Author) , Moyer, Richard W. (Author) , Watzl, Carsten (Author) , Hengel, Hartmut (Author) , Momburg, Frank (Author)
Format: Article (Journal)
Language:English
Published: August 25, 2011
In: PLoS pathogens
Year: 2011, Volume: 7, Issue: 8, Pages: 1-18
ISSN:1553-7374
DOI:10.1371/journal.ppat.1002195
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.ppat.1002195
Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1002195
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Author Notes:Mostafa Jarahian, Manuela Fiedler, André Cohnen, Dominik Djandji, Günter J. Hämmerling, Cornelius Gati, Adelheid Cerwenka, Peter C. Turner, Richard W. Moyer, Carsten Watzl, Hartmut Hengel, Frank Momburg
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Summary:Natural killer (NK) cells are an important element in the immune defense against the orthopox family members vaccinia virus (VV) and ectromelia virus (ECTV). NK cells are regulated through inhibitory and activating signaling receptors, the latter involving NKG2D and the natural cytotoxicity receptors (NCR), NKp46, NKp44 and NKp30. Here we report that VV infection results in an upregulation of ligand structures for NKp30 and NKp46 on infected cells, whereas the binding of NKp44 and NKG2D was not significantly affected. Likewise, infection with ectromelia virus (ECTV), the mousepox agent, enhanced binding of NKp30 and, to a lesser extent, NKp46. The hemagglutinin (HA) molecules from VV and ECTV, which are known virulence factors, were identified as novel ligands for NKp30 and NKp46. Using NK cells with selectively silenced NCR expression and NCR-CD3ζ reporter cells, we observed that HA present on the surface of VV-infected cells, or in the form of recombinant soluble protein, was able to block NKp30-triggered activation, whereas it stimulated the activation through NKp46. The net effect of this complex influence on NK cell activity resulted in a decreased NK lysis susceptibility of infected cells at late time points of VV infection when HA was expression was pronounced. We conclude that poxviral HA represents a conserved ligand of NCR, exerting a novel immune escape mechanism through its blocking effect on NKp30-mediated activation at a late stage of infection.
Item Description:Gesehen am 04.07.2022
Physical Description:Online Resource
ISSN:1553-7374
DOI:10.1371/journal.ppat.1002195

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