Interferon-γ and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells

被引:103
作者
de Lang, Anna [1 ]
Osterhaus, Albert D. M. E. [1 ]
Haagmans, Bart L. [1 ]
机构
[1] Erasmus MC, Dept Virol, NL-3015 GE Rotterdam, Netherlands
关键词
SARS-CoV; ACE2; interferon-gamma; interleukin-4;
D O I
10.1016/j.virol.2006.06.011
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Interferons (IFNs) inhibit severe acute respiratory syndrome coronavirus (SARS-CoV) replication and might be valuable for SARS treatment. In this study, we demonstrate that treatment of Vero E6 cells with interleukin-4 (IL-4) decreased the susceptibility of these cells to SARS-CoV infection. In contrast to IFNs, IL-4 did not show antiviral activity when administered immediately after SARS-CoV infection, suggesting that IL-4 acts early during the SARS-CoV replication cycle. Indeed, binding of recombinant SARS-CoV spike protein to Vero E6 cells was diminished on cells treated with IL-4, but also on cells exposed to IFN-gamma. Consistent with these observations, IL-4 and IFN-gamma downregulated cell surface expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Besides diminished ACE2 cell surface expression, ACE2 mRNA levels were also decreased after treatment with these cytokines. These findings suggest that IL-4 and IFN-gamma inhibit SARS-CoV` replication partly through downregulation of ACE2. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:474 / 481
页数:8
相关论文
共 40 条
[21]   Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome [J].
Kuiken, T ;
Fouchier, RAM ;
Schutten, M ;
Rimmelzwaan, GF ;
van Amerongen, G ;
van Riel, D ;
Laman, JD ;
de Jong, T ;
van Doornum, G ;
Lim, W ;
Ling, AE ;
Chan, PKS ;
Tam, JS ;
Zambon, MC ;
Gopal, R ;
Drosten, C ;
van der Werf, S ;
Escriou, N ;
Manuguerra, JC ;
Stöhr, K ;
Peiris, JSM ;
Osterhaus, ADME .
LANCET, 2003, 362 (9380) :263-270
[22]   Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus [J].
Li, WH ;
Moore, MJ ;
Vasilieva, N ;
Sui, JH ;
Wong, SK ;
Berne, MA ;
Somasundaran, M ;
Sullivan, JL ;
Luzuriaga, K ;
Greenough, TC ;
Choe, H ;
Farzan, M .
NATURE, 2003, 426 (6965) :450-454
[23]   IL-4 suppresses the expression and the replication of hepatitis B virus in the hepatocellular carcinoma cell line Hep3B [J].
Lin, SJ ;
Shu, PY ;
Chang, CM ;
Ng, AK ;
Hu, CP .
JOURNAL OF IMMUNOLOGY, 2003, 171 (09) :4708-4716
[24]   Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors [J].
Liu, SW ;
Xiao, GF ;
Chen, YB ;
He, YX ;
Niu, JK ;
Escalante, CR ;
Xiong, HB ;
Farmar, J ;
Debnath, AK ;
Tien, P ;
Jiang, SB .
LANCET, 2004, 363 (9413) :938-947
[25]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[26]  
LOHOFF M, 1990, J IMMUNOL, V144, P960
[27]   The genome sequence of the SARS-associated coronavirus [J].
Marra, MA ;
Jones, SJM ;
Astell, CR ;
Holt, RA ;
Brooks-Wilson, A ;
Butterfield, YSN ;
Khattra, J ;
Asano, JK ;
Barber, SA ;
Chan, SY ;
Cloutier, A ;
Coughlin, SM ;
Freeman, D ;
Girn, N ;
Griffith, OL ;
Leach, SR ;
Mayo, M ;
McDonald, H ;
Montgomery, SB ;
Pandoh, PK ;
Petrescu, AS ;
Robertson, AG ;
Schein, JE ;
Siddiqui, A ;
Smailus, DE ;
Stott, JE ;
Yang, GS ;
Plummer, F ;
Andonov, A ;
Artsob, H ;
Bastien, N ;
Bernard, K ;
Booth, TF ;
Bowness, D ;
Czub, M ;
Drebot, M ;
Fernando, L ;
Flick, R ;
Garbutt, M ;
Gray, M ;
Grolla, A ;
Jones, S ;
Feldmann, H ;
Meyers, A ;
Kabani, A ;
Li, Y ;
Normand, S ;
Stroher, U ;
Tipples, GA ;
Tyler, S .
SCIENCE, 2003, 300 (5624) :1399-1404
[28]   Interleukin-4 causes delayed virus clearance in influenza virus-infected mice [J].
Moran, TM ;
Isobe, H ;
FernandezSesma, A ;
Schulman, JL .
JOURNAL OF VIROLOGY, 1996, 70 (08) :5230-5235
[29]   Ribavirin and interferon-β synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines [J].
Morgenstern, B ;
Michaelis, M ;
Baer, PC ;
Doerr, HW ;
Cinatl, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 326 (04) :905-908
[30]   Lung pathology of fatal severe acute respiratory syndrome [J].
Nicholls, JM ;
Poon, LLM ;
Lee, KC ;
Ng, WF ;
Lai, ST ;
Leung, CY ;
Chu, CM ;
Hui, PK ;
Mak, KL ;
Lim, W ;
Yan, KW ;
Chan, KH ;
Tsang, NC ;
Guan, Y ;
Yuen, KY ;
Peiris, JSM .
LANCET, 2003, 361 (9371) :1773-1778