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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9287-9294 |
| Number of pages | 8 |
| Journal | Journal of Virology |
| Volume | 77 |
| Issue number | 17 |
| DOIs | |
| State | Published - Sep 1 2003 |
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ASJC Scopus subject areas
- Immunology
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Human cytomegalovirus US2 causes similar effects on both major histocompatibility complex class I and II proteins in epithelial and glial cells. / Hegde, Nagendra R.; Johnson, David.
In: Journal of Virology, Vol. 77, No. 17, 01.09.2003, p. 9287-9294.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Human cytomegalovirus US2 causes similar effects on both major histocompatibility complex class I and II proteins in epithelial and glial cells
AU - Hegde, Nagendra R.
AU - Johnson, David
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0042890427&partnerID=8YFLogxK
U2 - 10.1128/JVI.77.17.9287-9294.2003
DO - 10.1128/JVI.77.17.9287-9294.2003
M3 - Article
C2 - 12915544
AN - SCOPUS:0042890427
VL - 77
SP - 9287
EP - 9294
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 17
ER -