TY  - JOUR
AU  - Diab, Mohammad
AU  - Schmiedel, Dominik
AU  - Seidel, Einat
AU  - Bacharach, Eran
AU  - Mandelboim, Ofer
TI  - Human Metapneumovirus Escapes NK Cell Recognition through the Downregulation of Stress-Induced Ligands for NKG2D.
JO  - Viruses
VL  - 12
IS  - 7
SN  - 1999-4915
CY  - Basel
PB  - MDPI
M1  - DKFZ-2025-02451
SP  - 781
PY  - 2020
N1  - #DKFZ-MOST-Ca184#
AB  - The Pneumoviridae family includes human metapneumovirus (HMPV) and human orthopneumovirus, which is also known as a respiratory syncytial virus (HRSV). These are large enveloped, negative single-strand RNA viruses. HMPV and HRSV are the human members, which commonly infect children. HMPV, which was discovered in 2001, infects most children until the age of five, which causes an influenza-like illness. The interaction of this virus with immune cells is poorly understood. In this study, we show that HMPV evades natural killer (NK) cell attack by downregulating stress-induced ligands for the activating receptor NKG2D including: Major histocompatibility complex (MHC) class I polypeptide-related sequences A and B (MICA, MICB), UL16 binding proteins ULBP2, and ULBP3, but not ULBP1. Mechanistically, we show that the viral protein G is involved in the downregulation of ULBP2 and that the viral protein M2.2 is required for MICA and MICB downregulation. These findings emphasize the importance of NK cells, in general, and NKG2D, in particular, in controlling HMPV infection, which opens new avenues for treating HMPV.
KW  - Antibodies, Viral: immunology
KW  - Blotting, Western
KW  - Down-Regulation
KW  - Flow Cytometry
KW  - Humans
KW  - Killer Cells, Natural: immunology
KW  - Metapneumovirus: immunology
KW  - NK Cell Lectin-Like Receptor Subfamily K: immunology
KW  - Paramyxoviridae Infections: immunology
KW  - Real-Time Polymerase Chain Reaction
KW  - Viral Proteins: immunology
KW  - Pneumoviridae family (Other)
KW  - human metapneumovirus (HMPV) (Other)
KW  - natural killer (NK) (Other)
KW  - natural killer group 2D (NKG2D) (Other)
KW  - stress-induced ligands (Other)
KW  - Antibodies, Viral (NLM Chemicals)
KW  - KLRK1 protein, human (NLM Chemicals)
KW  - NK Cell Lectin-Like Receptor Subfamily K (NLM Chemicals)
KW  - Viral Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32698530
C2  - pmc:PMC7412239
DO  - DOI:10.3390/v12070781
UR  - https://inrepo02.dkfz.de/record/306222
ER  -