ArticlePLoS pathogens2021
The human cytomegalovirus protein UL147A downregulates the most prevalent MICA allele: MICA*008, to evade NK cell-mediated killing.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- The diverse functions of viral microproteins.bioRxiv : the preprint server for biology · 2026Article
- Longitudinal Dynamics of Soluble NKG2D Ligands in Mild and Moderate Coronavirus Disease-2019.Yonago acta medica · 2026Article
- The immune response to human cytomegalovirus: impact of age, co-morbidities and the significance of anti-viral activity assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Human Cytomegalovirus Immune Evasion of Natural Killer Cells: A Virus for All Seasons?Pathogens (Basel, Switzerland) · 2025Review
- Human cytomegalovirus: pathogenesis, prevention, and treatment.Molecular biomedicine · 2024Review
- Article
- HCMV-secreted glycoprotein gpUL4 inhibits TRAIL-mediated apoptosis and NK cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- CLPTM1L is a GPI-anchoring pathway component targeted by HCMV.The Journal of cell biology · 2023Article
- ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- High population frequencies ofFrontiers in immunology · 2023Article
- Suppression of MR1 by human cytomegalovirus inhibits MAIT cell activation.Frontiers in immunology · 2023Article
- Deciphering the Potential Coding of Human Cytomegalovirus: New Predicted Transmembrane Proteome.International journal of molecular sciences · 2022Article
- Review
- Evasion of the Host Immune Response by Betaherpesviruses.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells are innate immune lymphocytes capable of killing target cells without prior sensitization. One pivotal activating NK receptor is NKG2D, which binds a family of eight ligands, including the major histocompatibility complex (MHC) class I-related chain A (MICA). Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus causing morbidity and mortality in immunosuppressed patients and congenitally infected infants. HCMV encodes multiple antagonists of NK cell activation, including many mechanisms targeting MICA. However, only one of these mechanisms, the HCMV protein US9, counters the most prevalent MICA allele, MICA*008. Here, we discover that a hitherto uncharacterized HCMV protein, UL147A, specifically downregulates MICA*008. UL147A primarily induces MICA*008 maturation arrest, and additionally targets it to proteasomal degradation, acting additively with US9 during HCMV infection. Thus, UL147A hinders NKG2D-mediated elimination of HCMV-infected cells by NK cells. Mechanistic analyses disclose that the non-canonical GPI anchoring pathway of immature MICA*008 constitutes the determinant of UL147A specificity for this MICA allele. These findings advance our understanding of the complex and rapidly evolving HCMV immune evasion mechanisms, which may facilitate the development of antiviral drugs and vaccines.
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