Infected cell protein 47

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.

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).

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.

1. 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.
2. 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.
3. 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.