Endoplasmic reticulum chaperones participate in human cytomegalovirus US2-mediated degradation of class I major histocompatibility complex molecules.

The Journal of General Virology
Kristina Oresic, D Tortorella

Abstract

Inhibition of cell-surface expression of major histocompatibility complex class I molecules by human cytomegalovirus (HCMV, a beta-herpesvirus) promotes escape from recognition by CD8+ cytotoxic T cells. The HCMV US2 and US11 gene products induce class I downregulation during the early phase of HCMV infection by facilitating the degradation of class I heavy chains. The HCMV proteins promote the transport of the class I heavy chains across the endoplasmic reticulum (ER) membrane into the cytosol by a process referred to as 'dislocation', which is then followed by proteasome degradation. This process has striking similarities to the degradation of misfolded ER proteins mediated by ER quality control. Even though the major steps of the dislocation reaction have been characterized, the cellular proteins, specifically the ER chaperones involved in targeting class I for dislocation, have not been fully delineated. To elucidate the chaperones involved in HCMV-mediated class I dislocation, we utilized a chimeric class I heavy chain with an affinity tag at its carboxy terminus. Interestingly, US2 but not US11 continued to target the class I chimera for destruction, suggesting a structural limitation for US11-mediated degradation. Associ...Continue Reading

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Citations

Mar 29, 2012·Immunologic Research·Vanessa NoriegaDomenico Tortorella
Jan 13, 2009·Virology Journal·Mindy Miller-Kittrell, Tim E Sparer
Dec 24, 2013·Theory in Biosciences = Theorie in Den Biowissenschaften·Shipeng SunGuijian Liu
Mar 20, 2012·Biochimica Et Biophysica Acta·Zongwei Li, Zhuoyu Li
Jan 2, 2010·Seminars in Cell & Developmental Biology·Daniel C Chapman, David B Williams
Jun 7, 2014·Frontiers in Microbiology·Ellen Van Damme, Marnix Van Loock
Nov 10, 2015·Biotechnology and Applied Biochemistry·Hossein AghamollaeiGholamreza Farnoosh
Oct 14, 2021·Microbiology and Molecular Biology Reviews : MMBR·Evelyne KohliCarmen Garrido

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