PMID- 12368336
OWN - NLM
STAT- MEDLINE
DCOM- 20021126
LR  - 20190508
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 76
IP  - 21
DP  - 2002 Nov
TI  - Inhibition of HLA-DR assembly, transport, and loading by human cytomegalovirus 
      glycoprotein US3: a novel mechanism for evading major histocompatibility complex 
      class II antigen presentation.
PG  - 10929-41
AB  - Human cytomegalovirus (HCMV) establishes persistent lifelong infections and 
      replicates slowly. To withstand robust immunity, HCMV utilizes numerous immune 
      evasion strategies. The HCMV gene cassette encoding US2 to US11 encodes four 
      homologous glycoproteins, US2, US3, US6, and US11, that inhibit the major 
      histocompatibility complex class I (MHC-I) antigen presentation pathway, probably 
      inhibiting recognition by CD8(+) T lymphocytes. US2 also inhibits the MHC-II 
      antigen presentation pathway, causing degradation of human leukocyte antigen 
      (HLA)-DR-alpha and -DM-alpha and preventing recognition by CD4(+) T cells. We 
      investigated the effects of seven of the US2 to US11 glycoproteins on the MHC-II 
      pathway. Each of the glycoproteins was expressed by using replication-defective 
      adenovirus vectors. In addition to US2, US3 inhibited recognition of antigen by 
      CD4(+) T cells by a novel mechanism. US3 bound to class II alpha/beta complexes 
      in the endoplasmic reticulum (ER), reducing their association with Ii. Class II 
      molecules moved normally from the ER to the Golgi apparatus in US3-expressing 
      cells but were not sorted efficiently to the class II loading compartment. As a 
      consequence, formation of peptide-loaded class II complexes was reduced. We 
      concluded that US3 and US2 can collaborate to inhibit class II-mediated 
      presentation of endogenous HCMV antigens to CD4(+) T cells, allowing 
      virus-infected cells to resist recognition by CD4(+) T cells.
FAU - Hegde, Nagendra R
AU  - Hegde NR
AD  - Department of Molecular Microbiology and Immunology, Oregon Health and Science 
      University, Portland, Oregon 97239, USA.
FAU - Tomazin, Roman A
AU  - Tomazin RA
FAU - Wisner, Todd W
AU  - Wisner TW
FAU - Dunn, Claire
AU  - Dunn C
FAU - Boname, Jessica M
AU  - Boname JM
FAU - Lewinsohn, David M
AU  - Lewinsohn DM
FAU - Johnson, David C
AU  - Johnson DC
LA  - eng
GR  - R01 EY011245/EY/NEI NIH HHS/United States
GR  - EY11245/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Glycoproteins)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptides)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (US10 glycoprotein, Human herpesvirus 5)
RN  - 0 (US11 protein, herpesvirus)
RN  - 0 (US3 protein, cytomegalovirus)
RN  - 0 (US7 glycoprotein, Human herpesvirus 5)
RN  - 0 (US8 protein, Human herpesvirus 5)
RN  - 0 (US9 protein, Human herpesvirus 5)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Antigen Presentation/*immunology
MH  - Biological Transport
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cytomegalovirus/*immunology
MH  - Dimerization
MH  - Endoplasmic Reticulum/immunology
MH  - Glycoproteins/genetics/*immunology
MH  - Golgi Apparatus/immunology
MH  - HLA-DR Antigens/*immunology
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Humans
MH  - Immediate-Early Proteins/genetics/*immunology
MH  - Lysosomes
MH  - Membrane Glycoproteins/genetics/immunology
MH  - Membrane Proteins
MH  - Peptides/immunology
MH  - RNA-Binding Proteins/genetics/immunology
MH  - Subcellular Fractions
MH  - Tumor Cells, Cultured
MH  - Viral Proteins/genetics/immunology
PMC - PMC136637
EDAT- 2002/10/09 04:00
MHDA- 2002/11/28 04:00
PMCR- 2002/11/01
CRDT- 2002/10/09 04:00
PHST- 2002/10/09 04:00 [pubmed]
PHST- 2002/11/28 04:00 [medline]
PHST- 2002/10/09 04:00 [entrez]
PHST- 2002/11/01 00:00 [pmc-release]
AID - 0885 [pii]
AID - 10.1128/jvi.76.21.10929-10941.2002 [doi]
PST - ppublish
SO  - J Virol. 2002 Nov;76(21):10929-41. doi: 10.1128/jvi.76.21.10929-10941.2002.