Infected cell protein 47, also known as ICP47, is a protein expressed by large viruses (such as herpes simplex virus and cytomegalovirus) that enables them to evade the CD8 T-cell response of the human immune system. The secondary structure of Infected cell protein 47 has three helices.
Infected cell protein 47
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ICP47 specifically binds to the antigen processing associated transporter (TAP). TAP translocates antigenic peptides into the lumen of the endoplasmic reticulum (ER) for loading onto MHC class I molecules. This is an important step in the control of viral infections by CD8+ T cells. ICP47 is localized in the cytosol and acts as a high-affinity competitor for the peptide-binding site on TAP, thereby blocking peptide binding and translocation by TAP and subsequent loading of peptides onto MHC class I molecules (Matschulla T et al. 2017).
This prevents an infected cell from expressing viral epitopes on its surface (Goldsmith K et al. 1998). Subsequently, infected cells are masked to immune recognition by cytotoxic T lymphocytes (Berger C et al. 2000).
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Large DNA viruses have evolved numerous strategies to disrupt the MHC class I antigen presentation pathway. To date, five virally encoded inhibitors have been reported to directly block TAP function:
- ICP47(herpes simplex virus type-1, HSV-1)
- US6(human cytomegalovirus, HCMV),
- BNLF2a(Epstein-Barr virus, EBV),
- UL49.5(varicella-zoster virus) and
- CPXV12(smallpox virus).
ICP47 was originally observed as an early HSV-1 gene product that inhibits antigen presentation to CD8+ T cells and was the first TAP inhibitor described.
LiteratureThis section has been translated automatically.
- Berger C et al. (2000) Expression of herpes simplex virus ICP47 and human cytomegalovirus US11 prevents recognition of transgene products by CD8(+) cytotoxic T lymphocytes. Journal of Virology 74: 4465-4473.
- Goldsmith K et al (1998) Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response. The Journal of Experimental Medicine 187: 341-348.
- Matschulla T et al. (2017) A highly conserved sequence of the viral TAP inhibitor ICP47 is required for freezing of the peptide transport cycle. Sci Rep 7:2933.