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

AUTOR(ES)

Hegde, Nagendra R.

FONTE

American Society for Microbiology

RESUMO

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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