KDELR2 Competes with Measles Virus Envelope Proteins for Cellular Chaperones Reducing Their Chaperone-Mediated Cell Surface Transport

被引:5
作者
Tiwarekar, Vishakha [1 ]
Fehrholz, Markus [1 ,2 ]
Schneider-Schaulies, Juergen [1 ]
机构
[1] Univ Wurzburg, Inst Virol & Immunobiol, D-97078 Wurzburg, Germany
[2] Skin & Hair Res Solut GmbH, Monasterium Lab, D-48149 Munster, Germany
来源
VIRUSES-BASEL | 2019年 / 11卷 / 01期
关键词
measles virus; KDELR2; calnexin; GRP78; surface transport; ENDOPLASMIC-RETICULUM; APOBEC3G; RECEPTOR; EXPRESSION; STRESS; REPLICATION;
D O I
10.3390/v11010027
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Recently, we found that the cytidine deaminase APOBEC3G (A3G) inhibits measles (MV) replication. Using a microarray, we identified differential regulation of several host genes upon ectopic expression of A3G. One of the up-regulated genes, the endoplasmic reticulum (ER) protein retention receptor KDELR2, reduced MV replication similar to 5 fold when it was over-expressed individually in Vero and CEM-SS T cells. Silencing of KDELR2 in A3G-expressing Vero cells abrogated the antiviral activity induced by A3G, confirming its role as an A3G-regulated antiviral host factor. Recognition of the KDEL (Lys-Asp-Glu-Leu) motif by KDEL receptors initiates the retrograde transport of soluble proteins that have escaped the ER and play an important role in ER quality control. Although KDELR2 over-expression reduced MV titers in cell cultures, we observed no interaction between KDELR2 and the MV hemagglutinin (H) protein. Instead, KDELR2 retained chaperones in the ER, which are required for the correct folding and transport of the MV envelope glycoproteins H and fusion protein (F) to the cell surface. Our data indicate that KDELR2 competes with MV envelope proteins for binding to calnexin and GRP78/Bip, and that this interaction limits the availability of the chaperones for MV proteins, causing the reduction of virus spread and titers.
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页数:13
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共 35 条
  • [11] APOBEC3G has the ability to programme T cell plasticity
    Garg, Anuradha
    Kaul, Deepak
    [J]. BLOOD CELLS MOLECULES AND DISEASES, 2016, 59 : 108 - 112
  • [12] The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi
    Giannotta, Monica
    Ruggiero, Carmen
    Grossi, Mauro
    Cancino, Jorge
    Capitani, Mirco
    Pulvirenti, Teodoro
    Consoli, Grazia Maria Letizia
    Geraci, Corrada
    Fanelli, Francesca
    Luini, Alberto
    Sallese, Michele
    [J]. EMBO JOURNAL, 2012, 31 (13) : 2869 - 2881
  • [13] A BREFELDIN-A-LIKE PHENOTYPE IS INDUCED BY THE OVEREXPRESSION OF A HUMAN ERD-2-LIKE PROTEIN, ELP-1
    HSU, VW
    SHAH, N
    KLAUSNER, RD
    [J]. CELL, 1992, 69 (04) : 625 - 635
  • [14] How Viruses Use the Endoplasmic Reticulum for Entry, Replication, and Assembly
    Inoue, Takamasa
    Tsai, Billy
    [J]. COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2013, 5 (01):
  • [15] KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
    Kamimura, Daisuke
    Katsunuma, Kokichi
    Arima, Yasunobu
    Atsumi, Toru
    Jiang, Jing-jing
    Bando, Hidenori
    Meng, Jie
    Sabharwal, Lavannya
    Stofkova, Andrea
    Nishikawa, Naoki
    Suzuki, Hironao
    Ogura, Hideki
    Ueda, Naoko
    Tsuruoka, Mineko
    Harada, Masaya
    Kobayashi, Junya
    Hasegawa, Takanori
    Yoshida, Hisahiro
    Koseki, Haruhiko
    Miura, Ikuo
    Wakana, Shigeharu
    Nishida, Keigo
    Kitamura, Hidemitsu
    Fukada, Toshiyuki
    Hirano, Toshio
    Murakami, Masaaki
    [J]. NATURE COMMUNICATIONS, 2015, 6
  • [16] LIGAND-INDUCED REDISTRIBUTION OF A HUMAN KDEL RECEPTOR FROM THE GOLGI-COMPLEX TO THE ENDOPLASMIC-RETICULUM
    LEWIS, MJ
    PELHAM, HRB
    [J]. CELL, 1992, 68 (02) : 353 - 364
  • [17] KDEL Receptors Assist Dengue Virus Exit from the Endoplasmic Reticulum
    Li, Ming Yuan
    Grandadam, Marc
    Kwok, Kevin
    Lagache, Thibault
    Siu, Yu Lam
    Zhang, Jing Shu
    Sayteng, Kouxiong
    Kudelko, Mateusz
    Qin, Cheng Feng
    Olivo-Marin, Jean-Christophe
    Bruzzone, Roberto
    Wang, Pei Gang
    [J]. CELL REPORTS, 2015, 10 (09): : 1496 - 1507
  • [18] The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies
    Luo, B.
    Lee, A. S.
    [J]. ONCOGENE, 2013, 32 (07) : 805 - 818
  • [19] Recombinant measles viruses expressing altered hemagglutinin (H) genes: Functional separation of mutations determining H antibody escape from neurovirulence
    Moeller, K
    Duffy, I
    Duprex, P
    Rima, B
    Beschorner, R
    Fauser, S
    Meyermann, R
    Niewiesk, S
    Ter Meulen, V
    Schneider-Schaulies, J
    [J]. JOURNAL OF VIROLOGY, 2001, 75 (16) : 7612 - 7620
  • [20] A C-TERMINAL SIGNAL PREVENTS SECRETION OF LUMINAL ER PROTEINS
    MUNRO, S
    PELHAM, HRB
    [J]. CELL, 1987, 48 (05) : 899 - 907