The MHC class I homolog of human cytomegalovirus is resistant to down-regulation mediated by the unique short region protein (US)2, US3, US6, and US11 gene products

Boyoun Park, Hokyung Oh, Sungwook Lee, Yangsook Song, Jinwook Shin, Young Chul Sung, Sue Yun Hwang, Kwangseog Ahn

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Human CMV encodes four unique short region proteins (US), US2, US3, US6, and US11, each independently sufficient for causing the down-regulation of MHC class I molecules on the cell surface. This down-regulation allows infected cells to evade recognition by cytotoxic T cells but leaves them susceptible to NK cells, which lyse cells that lack class I molecules. Another human CMV-encoded protein, unique long region protein 18 (UL18), is an MHC class I homolog that might provide a mechanism for inhibiting the NK cell response. The sequence similarities between MHC class I molecules and UL18 along with the ability of UL18 to form trimeric complexes with β2-microglobulin and peptides led to the hypothesis that if the US and UL18 gene products coexist temporally during infection, the US proteins might down-regulate UL18 molecules, similar to their action on MHC class I molecules. We show here that temporal expression of US and UL18 genes partially overlaps during infection. However, unlike MHC class I molecules, the MHC class I homolog, UL18, is fully resistant to the down-regulation associated with the US2, US3, US6, and US11 gene products. The specific effect of US proteins on MHC class I molecules, but not on UL18, represents another example of how viral proteins have evolved to evade immune surveillance, avoiding fratricide by specifically targeting host proteins.

Original languageEnglish
Pages (from-to)3464-3469
Number of pages6
JournalJournal of Immunology
Volume168
Issue number7
DOIs
Publication statusPublished - 2002 Apr 1

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Cytomegalovirus
Down-Regulation
Genes
Proteins
Natural Killer Cells
Viral Proteins
Protein Transport
Infection
T-Lymphocytes
Peptides

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Park, Boyoun ; Oh, Hokyung ; Lee, Sungwook ; Song, Yangsook ; Shin, Jinwook ; Sung, Young Chul ; Hwang, Sue Yun ; Ahn, Kwangseog. / The MHC class I homolog of human cytomegalovirus is resistant to down-regulation mediated by the unique short region protein (US)2, US3, US6, and US11 gene products. In: Journal of Immunology. 2002 ; Vol. 168, No. 7. pp. 3464-3469.
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abstract = "Human CMV encodes four unique short region proteins (US), US2, US3, US6, and US11, each independently sufficient for causing the down-regulation of MHC class I molecules on the cell surface. This down-regulation allows infected cells to evade recognition by cytotoxic T cells but leaves them susceptible to NK cells, which lyse cells that lack class I molecules. Another human CMV-encoded protein, unique long region protein 18 (UL18), is an MHC class I homolog that might provide a mechanism for inhibiting the NK cell response. The sequence similarities between MHC class I molecules and UL18 along with the ability of UL18 to form trimeric complexes with β2-microglobulin and peptides led to the hypothesis that if the US and UL18 gene products coexist temporally during infection, the US proteins might down-regulate UL18 molecules, similar to their action on MHC class I molecules. We show here that temporal expression of US and UL18 genes partially overlaps during infection. However, unlike MHC class I molecules, the MHC class I homolog, UL18, is fully resistant to the down-regulation associated with the US2, US3, US6, and US11 gene products. The specific effect of US proteins on MHC class I molecules, but not on UL18, represents another example of how viral proteins have evolved to evade immune surveillance, avoiding fratricide by specifically targeting host proteins.",
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The MHC class I homolog of human cytomegalovirus is resistant to down-regulation mediated by the unique short region protein (US)2, US3, US6, and US11 gene products. / Park, Boyoun; Oh, Hokyung; Lee, Sungwook; Song, Yangsook; Shin, Jinwook; Sung, Young Chul; Hwang, Sue Yun; Ahn, Kwangseog.

In: Journal of Immunology, Vol. 168, No. 7, 01.04.2002, p. 3464-3469.

Research output: Contribution to journalArticle

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