scholarly journals Human Cytomegalovirus US2 Causes Similar Effects on Both Major Histocompatibility Complex Class I and II Proteins in Epithelial and Glial Cells

2003 ◽  
Vol 77 (17) ◽  
pp. 9287-9294 ◽  
Author(s):  
Nagendra R. Hegde ◽  
David C. Johnson
Keyword(s):  
Major Histocompatibility Complex ◽  
Human Cytomegalovirus ◽  
Adenovirus Vector ◽  
Class Ii ◽  
Class I ◽  
Major Histocompatibility ◽  
Biologically Relevant ◽  
Histocompatibility Complex ◽  
In Cells

ABSTRACT The human cytomegalovirus (HCMV) glycoprotein US2 specifically binds to major histocompatibility complex (MHC) class I heavy chain (HC) and class II proteins DRα and DMα, triggering their degradation by proteasomes. Effects of US2 on class II proteins were originally characterized in HCMV- or adenovirus vector-infected U373 astroglioma cells. Here, we have extended characterization of US2-mediated degradation of class II DRα to two other cell lines, including biologically relevant epithelial cells. Comparison of the effects of US2 in cells expressing both class I and II proteins demonstrated only a slight preference for class I HC. Moreover, US2 caused degradation of DRα and DMα when these proteins were expressed by transfection without DRβ, invariant chain (Ii), or DMβ. Therefore, US2 binds to α chains of DR and DM and triggers endoplasmic reticulum degradation without formation of class II DR αβ/Ii or DM αβ complexes. Similar levels of degradation of class II α were observed in cells expressing vastly different amounts of class II, suggesting that cellular factors, other than class II, were limiting. We concluded that US2 has broad effects in a variety of cells that express both class I and II proteins and is relevant to HCMV infection in vivo.

scholarly journals Human Cytomegalovirus-Encoded Immune Modulators Partner To Downregulate Major Histocompatibility Complex Class I Molecules

2008 ◽  
Vol 83 (3) ◽  
pp. 1359-1367 ◽  
Author(s):  
Vanessa M. Noriega ◽  
Domenico Tortorella
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Mhc Class I ◽  
Human Cytomegalovirus ◽  
Class I ◽  
Immune Recognition ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Presentation Pathway ◽  
In Cells

ABSTRACT Throughout the course of natural evolution with its host, the human cytomegalovirus (HCMV) has developed a variety of strategies to avoid immune recognition and clearance. The major histocompatibility complex (MHC) class I antigen presentation pathway is a major target of the virus. HCMV encodes at least six gene products that modulate the processing of endoplasmic reticulum (ER)-resident MHC class I molecules. Here, we show that two virus-encoded proteins, US2 and US3, coordinate their functions toward the common goal of attenuating class I protein surface expression. In cells stably expressing both US2 and US3, class I molecules were almost completely downregulated from the cell surface. In addition, pulse-chase analysis revealed that the proteasome-dependent turnover of class I molecules occurs more rapidly in cells expressing both US2 and US3 than either US2 or US3 alone. The ability of US3 to retain class I molecules in the ER produces a target-rich environment for US2 to mediate the destruction of class I heavy chains. In fact, expression of US3 enhanced the association between US2 and class I molecules, thus encouraging their dislocation and degradation. This immune evasion strategy ensures that viral antigens are not presented on the cell surface during the early phase of HCMV infection, a critical time of replication and viral proliferation.

scholarly journals Binding of Human Cytomegalovirus US2 to Major Histocompatibility Complex Class I and II Proteins Is Not Sufficient for Their Degradation

2002 ◽  
Vol 76 (16) ◽  
pp. 8265-8275 ◽  
Author(s):  
Mathieu S. Chevalier ◽  
Gwynn M. Daniels ◽  
David C. Johnson
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Human Cytomegalovirus ◽  
Class Ii ◽  
Degradation Pathway ◽  
Class I ◽  
Chimeric Proteins ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
C Terminus

ABSTRACT Human cytomegalovirus (HCMV) glycoprotein US2 causes degradation of major histocompatibility complex (MHC) class I heavy-chain (HC), class II DR-α and DM-α proteins, and HFE, a nonclassical MHC protein. In US2-expressing cells, MHC proteins present in the endoplasmic reticulum (ER) are degraded by cytosolic proteasomes. It appears that US2 binding triggers a normal cellular pathway by which misfolded or aberrant proteins are translocated from the ER to cytoplasmic proteasomes. To better understand how US2 binds MHC proteins and causes their degradation, we constructed a panel of US2 mutants. Mutants truncated from the N terminus as far as residue 40 or from the C terminus to amino acid 140 could bind to class I and class II proteins. Nevertheless, mutants lacking just the cytosolic tail (residues 187 to 199) were unable to cause degradation of both class I and II proteins. Chimeric proteins were constructed in which US2 sequences were replaced with homologous sequences from US3, an HCMV glycoprotein that can also bind to class I and II proteins. One of these US2/US3 chimeras bound to class II but not to class I, and a second bound class I HC better than wild-type US2. Therefore, US2 residues involved in the binding to MHC class I differ subtly from those involved in binding to class II proteins. Moreover, our results demonstrate that the binding of US2 to class I and II proteins is not sufficient to cause degradation of MHC proteins. The cytosolic tail of US2 and certain US2 lumenal sequences, which are not involved in binding to MHC proteins, are required for degradation. Our results are consistent with the hypothesis that US2 couples MHC proteins to components of the ER degradation pathway, enormously increasing the rate of degradation of MHC proteins.

Characterization of major histocompatibility complex class I, and class II DRB loci of captive and wild Indian leopards (Panthera pardus fusca)

Genetica ◽  
2017 ◽  
Vol 145 (6) ◽  
pp. 541-558
Author(s):  
Drashti R. Parmar ◽  
Siuli Mitra ◽  
Snehalata Bhadouriya ◽  
Tirupathi Rao ◽  
Vaishnavi Kunteepuram ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Class I ◽  
Panthera Pardus ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I AND CLASS II EXPRESSION BY MYOCYTES IN CARDIAC BIOPSIES POSTTRANSPLANTATION

1988 ◽  
Vol 45 (5) ◽  
pp. 972-978 ◽  
Author(s):  
A. AHMED-ANSARI ◽  
TALAAT S. TADROS ◽  
WILLIAM D. KNOPF ◽  
DOUGLAS A. MURPHY ◽  
GARY HERTZLER ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex
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