Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication

被引:188
|
作者
Martínez, MA
Gutiérrez, A
Armand-Ugón, M
Blanco, J
Parera, M
Gómez, J
Clotet, B
Esté, JA
机构
[1] Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Retrovirol Lab IrsiCaixa, Badalona 08916, Spain
[2] Univ Autonoma Barcelona, Dept Internal Med, Liver Unit, Hosp Gen Univ Vall Hebron, Barcelona 08035, Spain
关键词
co-receptors; CXCR4; CCR5; gene silencing; RNA interference;
D O I
10.1097/00002030-200212060-00002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objectives: Duplexes of 21 base pair RNA, known as short-interfering RNA (siRNA), have been shown to inhibit gene expression by a sequence-specific RNA degradation mechanism termed RNA interference (RNAi). The objective of our study was to evaluate the effect of chemokine receptor gene suppression by RNAi on the entry and replication of HIV-1. Methods: A flow cytometry and microscopy evaluation of HIV co-receptor expression of cells transfected with siRNA. An evaluation of the effect of siRNA on HIV entry and replication by intracellular p24 antigen detection, and virus production by infected cells, respectively. Results: siRNA that target CXCR4 and CCR5 could effectively impede cell surface protein expression and their consequent function as HIV co-receptors. The inhibitory effect of RNAi directed to CXCR4 was detected 48 h after transfection of CXCR4+ U87-CD4+ cells. The expression of CXCR4 and CCR5 was blocked in 63 and 48% of positive cells by the corresponding siRNA. However, siRNA directed to CXCR4 or CCR5 did not have an effect on CD4 cells or green fluorescence protein expression. siRNA directed to CXCR4 did not suppress CCR5 expression or vice versa. The suppression of HIV-1 co-receptor expression effectively blocked the acute infection of CXCR4+ or CCR5+ U87-CD4+ cells by X4 (NL4-3) or R5 (BaL) HIV-1 strains. Inhibition of virus replication occurred regardless of the multiplicity. of infection employed. Conclusion: Our results demonstrate that RNAi may be used to block HIV entry and replication through the blockade of cellular gene expression. Gene silencing by siRNA may become a valid alternative for HIV intervention. (C) 2002 Lippincott Williams Wilkins.
引用
收藏
页码:2385 / 2390
页数:6
相关论文
共 50 条
  • [1] Inhibition of HIV-1 replication by RNA interference of p53 expression
    Pauls, Eduardo
    Senserrich, Jordi
    Clotet, Bonaventura
    Este, Jose A.
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 80 (03) : 659 - 667
  • [2] Suppression of HIV replication using RNA interference against HIV-1 integrase
    Lau, Tat San
    Li, Yonggang
    Kameoka, Masanori
    Ng, Tzi Bun
    Wan, David Chi Cheong
    [J]. FEBS LETTERS, 2007, 581 (17) : 3253 - 3259
  • [3] Control of HIV-1 replication by RNA interference
    Lee, NS
    Rossi, JJ
    [J]. VIRUS RESEARCH, 2004, 102 (01) : 53 - 58
  • [4] Modulation of HIV-1 replication by RNA interference
    Jacque, JM
    Triques, K
    Stevenson, M
    [J]. NATURE, 2002, 418 (6896) : 435 - 438
  • [5] Modulation of HIV-1 replication by RNA interference
    Jean-Marc Jacque
    Karine Triques
    Mario Stevenson
    [J]. Nature, 2002, 418 : 435 - 438
  • [6] Cytokine modulation of HIV-1 chemokine receptor expression
    Alan L. Landay
    Bruce Patterson
    Jan Andersson
    [J]. Nature Medicine, 1999, 5 : 592 - 592
  • [7] Cytokine modulation of HIV-1 chemokine receptor expression
    Margolis, L
    Grivel, JC
    [J]. NATURE MEDICINE, 1999, 5 (06) : 592 - 593
  • [8] Relationship between chemokine receptor expression, chemokine levels and HIV-1 replication in the lungs of persons exposed to Mycobacterium tuberculosis
    Kalsdorf, Barbara
    Skolimowska, Keira H.
    Scriba, Thomas J.
    Dawson, Rod
    Dheda, Keertan
    Wood, Kathryn
    Hofmeister, Jessica
    Hanekom, Willem A.
    Lange, Christoph
    Wilkinson, Robert J.
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2013, 43 (02) : 540 - 549
  • [9] Inhibition of HIV-1 Replication by RNA-Based Strategies
    Reyes-Darias, Jose A.
    Sanchez-Luque, Francisco J.
    Berzal-Herranz, Alfredo
    [J]. CURRENT HIV RESEARCH, 2008, 6 (06) : 500 - 514
  • [10] Inhibition of drug-resistant HIV-1 by RNA interference
    Huelsmann, PM
    Rauch, P
    Allers, K
    John, MJ
    Metzner, KJ
    [J]. ANTIVIRAL RESEARCH, 2006, 69 (01) : 1 - 8