Human cytomegalovirus UL18 utilizes US6 for evading the NK and T-cell responses

Youngkyun Kim, Boyoun Park, Sunglim Cho, Jinwook Shin, Kwangmin Cho, Youngsoo Jun, Kwangseog Ahn

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) US6 glycoprotein inhibits TAP function, resulting in down-regulation of MHC class I molecules at the cell surface. Cells lacking MHC class I molecules are susceptible to NK cell lysis. HCMV expresses UL18, a MHC class I homolog that functions as a surrogate to prevent host cell lysis. Despite a high level of sequence and structural homology between UL18 and MHC class I molecules, surface expression of MHC class I, but not UL18, is down regulated by US6. Here, we describe a mechanism of action by which HCMV UL18 avoids attack by the self-derived TAP inhibitor US6. UL18 abrogates US6 inhibition of ATP binding by TAP and, thereby, restores TAP-mediated peptide translocation. In addition, UL18 together with US6 interferes with the physical association between MHC class I molecules and TAP that is required for optimal peptide loading. Thus, regardless of the recovery of TAP function, surface expression of MHC class I molecules remains decreased. UL18 represents a unique immune evasion protein that has evolved to evade both the NK and the T cell immune responses.

Original languageEnglish
Article numbere1000123
JournalPLoS Pathogens
Volume4
Issue number8
DOIs
Publication statusPublished - 2008 Aug 1

Fingerprint

Cytomegalovirus
Natural Killer Cells
trypsinogen activation peptide
T-Lymphocytes
Immune Evasion
Recovery of Function
Sequence Homology
Glycoproteins
Down-Regulation
Adenosine Triphosphate
Peptides
Proteins

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Kim, Youngkyun ; Park, Boyoun ; Cho, Sunglim ; Shin, Jinwook ; Cho, Kwangmin ; Jun, Youngsoo ; Ahn, Kwangseog. / Human cytomegalovirus UL18 utilizes US6 for evading the NK and T-cell responses. In: PLoS Pathogens. 2008 ; Vol. 4, No. 8.
@article{b75b6ac213dc44b69c21b056eca7a778,
title = "Human cytomegalovirus UL18 utilizes US6 for evading the NK and T-cell responses",
abstract = "Human cytomegalovirus (HCMV) US6 glycoprotein inhibits TAP function, resulting in down-regulation of MHC class I molecules at the cell surface. Cells lacking MHC class I molecules are susceptible to NK cell lysis. HCMV expresses UL18, a MHC class I homolog that functions as a surrogate to prevent host cell lysis. Despite a high level of sequence and structural homology between UL18 and MHC class I molecules, surface expression of MHC class I, but not UL18, is down regulated by US6. Here, we describe a mechanism of action by which HCMV UL18 avoids attack by the self-derived TAP inhibitor US6. UL18 abrogates US6 inhibition of ATP binding by TAP and, thereby, restores TAP-mediated peptide translocation. In addition, UL18 together with US6 interferes with the physical association between MHC class I molecules and TAP that is required for optimal peptide loading. Thus, regardless of the recovery of TAP function, surface expression of MHC class I molecules remains decreased. UL18 represents a unique immune evasion protein that has evolved to evade both the NK and the T cell immune responses.",
author = "Youngkyun Kim and Boyoun Park and Sunglim Cho and Jinwook Shin and Kwangmin Cho and Youngsoo Jun and Kwangseog Ahn",
year = "2008",
month = "8",
day = "1",
doi = "10.1371/journal.ppat.1000123",
language = "English",
volume = "4",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "8",

}

Human cytomegalovirus UL18 utilizes US6 for evading the NK and T-cell responses. / Kim, Youngkyun; Park, Boyoun; Cho, Sunglim; Shin, Jinwook; Cho, Kwangmin; Jun, Youngsoo; Ahn, Kwangseog.

In: PLoS Pathogens, Vol. 4, No. 8, e1000123, 01.08.2008.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human cytomegalovirus UL18 utilizes US6 for evading the NK and T-cell responses

AU - Kim, Youngkyun

AU - Park, Boyoun

AU - Cho, Sunglim

AU - Shin, Jinwook

AU - Cho, Kwangmin

AU - Jun, Youngsoo

AU - Ahn, Kwangseog

PY - 2008/8/1

Y1 - 2008/8/1

N2 - Human cytomegalovirus (HCMV) US6 glycoprotein inhibits TAP function, resulting in down-regulation of MHC class I molecules at the cell surface. Cells lacking MHC class I molecules are susceptible to NK cell lysis. HCMV expresses UL18, a MHC class I homolog that functions as a surrogate to prevent host cell lysis. Despite a high level of sequence and structural homology between UL18 and MHC class I molecules, surface expression of MHC class I, but not UL18, is down regulated by US6. Here, we describe a mechanism of action by which HCMV UL18 avoids attack by the self-derived TAP inhibitor US6. UL18 abrogates US6 inhibition of ATP binding by TAP and, thereby, restores TAP-mediated peptide translocation. In addition, UL18 together with US6 interferes with the physical association between MHC class I molecules and TAP that is required for optimal peptide loading. Thus, regardless of the recovery of TAP function, surface expression of MHC class I molecules remains decreased. UL18 represents a unique immune evasion protein that has evolved to evade both the NK and the T cell immune responses.

AB - Human cytomegalovirus (HCMV) US6 glycoprotein inhibits TAP function, resulting in down-regulation of MHC class I molecules at the cell surface. Cells lacking MHC class I molecules are susceptible to NK cell lysis. HCMV expresses UL18, a MHC class I homolog that functions as a surrogate to prevent host cell lysis. Despite a high level of sequence and structural homology between UL18 and MHC class I molecules, surface expression of MHC class I, but not UL18, is down regulated by US6. Here, we describe a mechanism of action by which HCMV UL18 avoids attack by the self-derived TAP inhibitor US6. UL18 abrogates US6 inhibition of ATP binding by TAP and, thereby, restores TAP-mediated peptide translocation. In addition, UL18 together with US6 interferes with the physical association between MHC class I molecules and TAP that is required for optimal peptide loading. Thus, regardless of the recovery of TAP function, surface expression of MHC class I molecules remains decreased. UL18 represents a unique immune evasion protein that has evolved to evade both the NK and the T cell immune responses.

UR - http://www.scopus.com/inward/record.url?scp=50849088309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50849088309&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1000123

DO - 10.1371/journal.ppat.1000123

M3 - Article

C2 - 18688275

AN - SCOPUS:50849088309

VL - 4

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 8

M1 - e1000123

ER -