Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 315 (5818): 1579-1582

Copyright © 2007 by the American Association for the Advancement of Science

Suppression of MicroRNA-Silencing Pathway by HIV-1 During Virus Replication

Robinson Triboulet,1 Bernard Mari,3 Yea-Lih Lin,2 Christine Chable-Bessia,1 Yamina Bennasser,5 Kevin Lebrigand,3 Bruno Cardinaud,3 Thomas Maurin,3 Pascal Barbry,3 Vincent Baillat,4 Jacques Reynes,4 Pierre Corbeau,2 Kuan-Teh Jeang,5 Monsef Benkirane1*

Abstract: MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 19 to 25 nucleotides that function as gene regulators and as a host cell defense against both RNA and DNA viruses. We provide evidence for a physiological role of the miRNA-silencing machinery in controlling HIV-1 replication. Type III RNAses Dicer and Drosha, responsible for miRNA processing, inhibited virus replication both in peripheral blood mononuclear cells from HIV-1–infected donors and in latently infected cells. In turn, HIV-1 actively suppressed the expression of the polycistronic miRNA cluster miR-17/92. This suppression was found to be required for efficient viral replication and was dependent on the histone acetyltransferase Tat cofactor PCAF. Our results highlight the involvement of the miRNA-silencing pathway in HIV-1 replication and latency.

1 Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, Montpellier, France.
2 Laboratoire des Lentivirus et Transfert de Gènes, Institut de Génétique Humaine, Montpellier, France.
3 Institut de Pharmacologie Moléculaire et Cellulaire, UMR6097 CNRS/UNSA, Sophia Antipolis, France.
4 Service des Maladies Infectieuses et Tropicales, Hôpital Gui de Chauliac, Montpellier, France.
5 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

* To whom correspondence should be addressed. E-mail: bmonsef{at}igh.cnrs.fr


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Robust RNAi enhancement via human Argonaute-2 overexpression from plasmids, viral vectors and cell lines.
K. Borner, D. Niopek, G. Cotugno, M. Kaldenbach, T. Pankert, J. Willemsen, X. Zhang, N. Schurmann, S. Mockenhaupt, A. Serva, et al. (2013)
Nucleic Acids Res. 41, e199
   Abstract »    Full Text »    PDF »
RNA viruses and microRNAs: challenging discoveries for the 21st century.
G. Swaminathan, J. Martin-Garcia, and S. Navas-Martin (2013)
Physiol Genomics 45, 1035-1048
   Abstract »    Full Text »    PDF »
Exploring the role of human miRNAs in virus-host interactions using systematic overlap analysis.
Z. Li, X. Cui, F. Li, P. Li, M. Ni, S. Wang, and X. Bo (2013)
Bioinformatics 29, 2375-2379
   Abstract »    Full Text »    PDF »
MicroRNAs: History, Biogenesis, and Their Evolving Role in Animal Development and Disease.
M. Bhaskaran and M. Mohan (2013)
Veterinary Pathology
   Abstract »    Full Text »    PDF »
Human MicroRNA hsa-miR-296-5p Suppresses Enterovirus 71 Replication by Targeting the Viral Genome.
Z. Zheng, X. Ke, M. Wang, S. He, Q. Li, C. Zheng, Z. Zhang, Y. Liu, and H. Wang (2013)
J. Virol. 87, 5645-5656
   Abstract »    Full Text »    PDF »
In-Depth Analysis of the Interaction of HIV-1 with Cellular microRNA Biogenesis and Effector Mechanisms.
A. W. Whisnant, H. P. Bogerd, O. Flores, P. Ho, J. G. Powers, N. Sharova, M. Stevenson, C.-H. Chen, and B. R. Cullen (2013)
mBio 4, e00193-13
   Abstract »    Full Text »    PDF »
Next-Generation Sequencing of Small RNAs from HIV-Infected Cells Identifies Phased microRNA Expression Patterns and Candidate Novel microRNAs Differentially Expressed upon Infection.
S. T. Chang, M. J. Thomas, P. Sova, R. R. Green, R. E. Palermo, and M. G. Katze (2013)
mBio 4, e00549-12
   Abstract »    Full Text »    PDF »
miR-15a and miR-16 affect the angiogenesis of multiple myeloma by targeting VEGF.
C.-Y. Sun, X.-M. She, Y. Qin, Z.-B. Chu, L. Chen, L.-S. Ai, L. Zhang, and Y. Hu (2013)
Carcinogenesis 34, 426-435
   Abstract »    Full Text »    PDF »
The extent of sequence complementarity correlates with the potency of cellular miRNA-mediated restriction of HIV-1.
L. Houzet, Z. Klase, M. L. Yeung, A. Wu, S.-Y. Le, M. Quinones, and K.-T. Jeang (2012)
Nucleic Acids Res. 40, 11684-11696
   Abstract »    Full Text »    PDF »
Functional Analysis of a Crustacean MicroRNA in Host-Virus Interactions.
T. Huang and X. Zhang (2012)
J. Virol. 86, 12997-13004
   Abstract »    Full Text »    PDF »
MicroRNAs and HIV-1: Complex Interactions.
Z. Klase, L. Houzet, and K.-T. Jeang (2012)
J. Biol. Chem. 287, 40884-40890
   Abstract »    Full Text »    PDF »
HIV-1 Replication and APOBEC3 Antiviral Activity Are Not Regulated by P Bodies.
P. K. Phalora, N. M. Sherer, S. M. Wolinsky, C. M. Swanson, and M. H. Malim (2012)
J. Virol. 86, 11712-11724
   Abstract »    Full Text »    PDF »
Respiratory syncytial virus modifies microRNAs regulating host genes that affect virus replication.
A. Bakre, P. Mitchell, J. K. Coleman, L. P. Jones, G. Saavedra, M. Teng, S. M. Tompkins, and R. A. Tripp (2012)
J. Gen. Virol. 93, 2346-2356
   Abstract »    Full Text »    PDF »
RNA silencing as a cellular defense against HIV-1 infection: progress and issues.
V. R. Sanghvi and L. F. Steel (2012)
FASEB J 26, 3937-3945
   Abstract »    Full Text »    PDF »
Murine cytomegalovirus infection of cultured mouse cells induces expression of miR-7a.
A. Dittmer and K. Forstemann (2012)
J. Gen. Virol. 93, 1537-1547
   Abstract »    Full Text »    PDF »
Stable changes in CD4+ T lymphocyte miRNA expression after exposure to HIV-1.
F. Bignami, E. Pilotti, L. Bertoncelli, P. Ronzi, M. Gulli, N. Marmiroli, G. Magnani, M. Pinti, L. Lopalco, C. Mussini, et al. (2012)
Blood 119, 6259-6267
   Abstract »    Full Text »    PDF »
Differential Regulation of the Let-7 Family of MicroRNAs in CD4+ T Cells Alters IL-10 Expression.
S. Swaminathan, K. Suzuki, N. Seddiki, W. Kaplan, M. J. Cowley, C. L. Hood, J. L. Clancy, D. D. Murray, C. Mendez, L. Gelgor, et al. (2012)
J. Immunol. 188, 6238-6246
   Abstract »    Full Text »    PDF »
Deployment of the human immunodeficiency virus type 1 protein arsenal: combating the host to enhance viral transcription and providing targets for therapeutic development.
S. Dahiya, M. R. Nonnemacher, and B. Wigdahl (2012)
J. Gen. Virol. 93, 1151-1172
   Abstract »    Full Text »    PDF »
Achieving a cure for HIV infection: do we have reasons to be optimistic?.
V. Le Douce, A. Janossy, H. Hallay, S. Ali, R. Riclet, O. Rohr, and C. Schwartz (2012)
J. Antimicrob. Chemother. 67, 1063-1074
   Abstract »    Full Text »    PDF »
Regulation of Cyclin T1 and HIV-1 Replication by MicroRNAs in Resting CD4+ T Lymphocytes.
K. Chiang, T.-L. Sung, and A. P. Rice (2012)
J. Virol. 86, 3244-3252
   Abstract »    Full Text »    PDF »
Interplay between HIV-1 infection and host microRNAs.
G. Sun, H. Li, X. Wu, M. Covarrubias, L. Scherer, K. Meinking, B. Luk, P. Chomchan, J. Alluin, A. F. Gombart, et al. (2012)
Nucleic Acids Res. 40, 2181-2196
   Abstract »    Full Text »    PDF »
Murine cytomegalovirus encodes a miR-27 inhibitor disguised as a target.
V. Libri, A. Helwak, P. Miesen, D. Santhakumar, J. G. Borger, G. Kudla, F. Grey, D. Tollervey, and A. H. Buck (2012)
PNAS 109, 279-284
   Abstract »    Full Text »    PDF »
The Cellular TAR RNA Binding Protein, TRBP, Promotes HIV-1 Replication Primarily by Inhibiting the Activation of Double-Stranded RNA-Dependent Kinase PKR.
V. R. Sanghvi and L. F. Steel (2011)
J. Virol. 85, 12614-12621
   Abstract »    Full Text »    PDF »
HIV-1 Tat Protein Promotes Neuronal Dysfunction through Disruption of MicroRNAs.
J. R. Chang, R. Mukerjee, A. Bagashev, L. Del Valle, T. Chabrashvili, B. J. Hawkins, J. J. He, and B. E. Sawaya (2011)
J. Biol. Chem. 286, 41125-41134
   Abstract »    Full Text »    PDF »
Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection.
X. Peng, L. Gralinski, M. T. Ferris, M. B. Frieman, M. J. Thomas, S. Proll, M. J. Korth, J. R. Tisoncik, M. Heise, S. Luo, et al. (2011)
mBio 2, e00198-11
   Abstract »    Full Text »    PDF »
MiR-129-5p is required for histone deacetylase inhibitor-induced cell death in thyroid cancer cells.
P. Brest, S. Lassalle, V. Hofman, O. Bordone, V. Gavric Tanga, C. Bonnetaud, C. Moreilhon, G. Rios, J. Santini, P. Barbry, et al. (2011)
Endocr. Relat. Cancer 18, 711-719
   Abstract »    Full Text »    PDF »
Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4+ T Cell Line.
S. T. Chang, P. Sova, X. Peng, J. Weiss, G. L. Law, R. E. Palermo, and M. G. Katze (2011)
mBio 2, e00134-11
   Abstract »    Full Text »    PDF »
Viruses and microRNAs: RISCy interactions with serious consequences.
B. R. Cullen (2011)
Genes & Dev. 25, 1881-1894
   Abstract »    Full Text »    PDF »
Can the microRNA signature distinguish between thyroid tumors of uncertain malignant potential and other well-differentiated tumors of the thyroid gland?.
S. Lassalle, V. Hofman, M. Ilie, C. Bonnetaud, M.-P. Puissegur, P. Brest, C. Loubatier, N. Guevara, O. Bordone, B. Cardinaud, et al. (2011)
Endocr. Relat. Cancer 18, 579-594
   Abstract »    Full Text »    PDF »
Genome-wide screening using RNA interference to study host factors in viral replication and pathogenesis.
L. Houzet and K.-T. Jeang (2011)
Experimental Biology and Medicine 236, 962-967
   Abstract »    Full Text »    PDF »
MicroRNAs in Development and Disease.
D. Sayed and M. Abdellatif (2011)
Physiol Rev 91, 827-887
   Abstract »    Full Text »    PDF »
Virally induced changes in cellular microRNAs maintain latency of human cytomegalovirus in CD34+ progenitors.
E. Poole, S. R. McGregor Dallas, J. Colston, R. S. V. Joseph, and J. Sinclair (2011)
J. Gen. Virol. 92, 1539-1549
   Abstract »    Full Text »    PDF »
P Bodies Inhibit Retrotransposition of Endogenous Intracisternal A Particles.
C. Lu, X. Contreras, and B. M. Peterlin (2011)
J. Virol. 85, 6244-6251
   Abstract »    Full Text »    PDF »
MicroRNA fate upon targeting with anti-miRNA oligonucleotides as revealed by an improved Northern-blot-based method for miRNA detection.
A. G. Torres, M. M. Fabani, E. Vigorito, and M. J. Gait (2011)
RNA 17, 933-943
   Abstract »    Full Text »    PDF »
Temporal microRNA expression during in vitro myogenic progenitor cell proliferation and differentiation: regulation of proliferation by miR-682.
Y. Chen, J. Gelfond, L. M. McManus, and P. K. Shireman (2011)
Physiol Genomics 43, 621-630
   Abstract »    Full Text »    PDF »
Silencing microRNA by interfering nanoparticles in mice.
J. Su, H. Baigude, J. McCarroll, and T. M. Rana (2011)
Nucleic Acids Res. 39, e38
   Abstract »    Full Text »    PDF »
Diverging Affinity of Tospovirus RNA Silencing Suppressor Proteins, NSs, for Various RNA Duplex Molecules.
E. Schnettler, H. Hemmes, R. Huismann, R. Goldbach, M. Prins, and R. Kormelink (2010)
J. Virol. 84, 11542-11554
   Abstract »    Full Text »    PDF »
Absence of DICER in Monocytes and Its Regulation by HIV-1.
W. Coley, R. Van Duyne, L. Carpio, I. Guendel, K. Kehn-Hall, S. Chevalier, A. Narayanan, T. Luu, N. Lee, Z. Klase, et al. (2010)
J. Biol. Chem. 285, 31930-31943
   Abstract »    Full Text »    PDF »
HIV-1 regulation of latency in the monocyte-macrophage lineage and in CD4+ T lymphocytes.
L. Redel, V. Le Douce, T. Cherrier, C. Marban, A. Janossy, D. Aunis, C. Van Lint, O. Rohr, and C. Schwartz (2010)
J. Leukoc. Biol. 87, 575-588
   Abstract »    Full Text »    PDF »
Epigenetic Regulation of Kaposi's Sarcoma-Associated Herpesvirus Latency by Virus-Encoded MicroRNAs That Target Rta and the Cellular Rbl2-DNMT Pathway.
F. Lu, W. Stedman, M. Yousef, R. Renne, and P. M. Lieberman (2010)
J. Virol. 84, 2697-2706
   Abstract »    Full Text »    PDF »
Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection.
A. H. Buck, J. Perot, M. A. Chisholm, D. S. Kumar, L. Tuddenham, V. Cognat, L. Marcinowski, L. Dolken, and S. Pfeffer (2010)
RNA 16, 307-315
   Abstract »    Full Text »    PDF »
Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour encapsidation of HIV-1 genomic RNA.
L. G. Abrahamyan, L. Chatel-Chaix, L. Ajamian, M. P. Milev, A. Monette, J.-F. Clement, R. Song, M. Lehmann, L. DesGroseillers, M. Laughrea, et al. (2010)
J. Cell Sci. 123, 369-383
   Abstract »    Full Text »    PDF »
Upregulation of STAT3 Marks Burkitt Lymphoma Cells Refractory to Epstein-Barr Virus Lytic Cycle Induction by HDAC Inhibitors.
D. Daigle, C. Megyola, A. El-Guindy, L. Gradoville, D. Tuck, G. Miller, and S. Bhaduri-McIntosh (2010)
J. Virol. 84, 993-1004
   Abstract »    Full Text »    PDF »
Functional Analysis of a Cellular MicroRNA in Insect Host-Ascovirus Interaction.
M. Hussain and S. Asgari (2010)
J. Virol. 84, 612-620
   Abstract »    Full Text »    PDF »
Differential RNA silencing suppression activity of NS1 proteins from different influenza A virus strains.
W. de Vries, J. Haasnoot, R. Fouchier, P. de Haan, and B. Berkhout (2009)
J. Gen. Virol. 90, 1916-1922
   Abstract »    Full Text »    PDF »
Herpes Simplex Virus Type 1 Suppresses RNA-Induced Gene Silencing in Mammalian Cells.
Z. Wu, Y. Zhu, D. M. Bisaro, and D. S. Parris (2009)
J. Virol. 83, 6652-6663
   Abstract »    Full Text »    PDF »
The role of RNAi and microRNAs in animal virus replication and antiviral immunity.
J. L. Umbach and B. R. Cullen (2009)
Genes & Dev. 23, 1151-1164
   Abstract »    Full Text »    PDF »
Cellular versus viral microRNAs in host-virus interaction.
Z. Ghosh, B. Mallick, and J. Chakrabarti (2009)
Nucleic Acids Res. 37, 1035-1048
   Abstract »    Full Text »    PDF »
The NS3 protein of rice hoja blanca virus complements the RNAi suppressor function of HIV-1 Tat.
E. Schnettler, W. de Vries, H. Hemmes, J. Haasnoot, R. Kormelink, R. Goldbach, and B. Berkhout (2009)
EMBO Rep. 10, 258-263
   Abstract »    Full Text »    PDF »
The A-rich RNA sequences of HIV-1 pol are important for the synthesis of viral cDNA.
C. P. Keating, M. K. Hill, D. J. Hawkes, R. P. Smyth, C. Isel, S.-Y. Le, A. C. Palmenberg, J. A. Marshall, R. Marquet, G. J. Nabel, et al. (2009)
Nucleic Acids Res. 37, 945-956
   Abstract »    Full Text »    PDF »
HIV-1 Tat RNA silencing suppressor activity is conserved across kingdoms and counteracts translational repression of HIV-1.
S. Qian, X. Zhong, L. Yu, B. Ding, P. de Haan, and K. Boris-Lawrie (2009)
PNAS 106, 605-610
   Abstract »    Full Text »    PDF »
Human Cytomegalovirus Infection Alters the Expression of Cellular MicroRNA Species That Affect Its Replication.
F.-Z. Wang, F. Weber, C. Croce, C.-G. Liu, X. Liao, and P. E. Pellett (2008)
J. Virol. 82, 9065-9074
   Abstract »    Full Text »    PDF »
Closed Chromatin Architecture Is Induced by an RNA Duplex Targeting the HIV-1 Promoter Region.
K. Suzuki, T. Juelich, H. Lim, T. Ishida, T. Watanebe, D. A. Cooper, S. Rao, and A. D. Kelleher (2008)
J. Biol. Chem. 283, 23353-23363
   Abstract »    Full Text »    PDF »
Liver-Specific MicroRNA miR-122 Enhances the Replication of Hepatitis C Virus in Nonhepatic Cells.
J. Chang, J.-T. Guo, D. Jiang, H. Guo, J. M. Taylor, and T. M. Block (2008)
J. Virol. 82, 8215-8223
   Abstract »    Full Text »    PDF »
Virus meets RNAi: Symposium on Antiviral Applications of RNA Interference.
R. P. van Rij (2008)
EMBO Rep. 9, 725-729
   Full Text »    PDF »
Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element.
D. L. Ouellet, I. Plante, P. Landry, C. Barat, M.-E. Janelle, L. Flamand, M. J. Tremblay, and P. Provost (2008)
Nucleic Acids Res. 36, 2353-2365
   Abstract »    Full Text »    PDF »
Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver.
J. Elmen, M. Lindow, A. Silahtaroglu, M. Bak, M. Christensen, A. Lind-Thomsen, M. Hedtjarn, J. B. Hansen, H. F. Hansen, E. M. Straarup, et al. (2008)
Nucleic Acids Res. 36, 1153-1162
   Abstract »    Full Text »    PDF »
Primary T-lymphocytes rescue the replication of HIV-1 DIS RNA mutants in part by facilitating reverse transcription.
K. L. Jones, S. Sonza, and J. Mak (2008)
Nucleic Acids Res. 36, 1578-1588
   Abstract »    Full Text »    PDF »
MicroRNA expression profiling in classic Hodgkin lymphoma.
A. Navarro, A. Gaya, A. Martinez, A. Urbano-Ispizua, A. Pons, O. Balague, B. Gel, P. Abrisqueta, A. Lopez-Guillermo, R. Artells, et al. (2008)
Blood 111, 2825-2832
   Abstract »    Full Text »    PDF »
miR-122 targeting with LNA/2'-O-methyl oligonucleotide mixmers, peptide nucleic acids (PNA), and PNA-peptide conjugates.
M. M. Fabani and M. J. Gait (2008)
RNA 14, 336-346
   Abstract »    Full Text »    PDF »
The Receptor Tyrosine Kinase RON Represses HIV-1 Transcription by Targeting RNA Polymerase II Processivity.
A. Klatt, Z. Zhang, P. Kalantari, P. A. Hankey, D. S. Gilmour, and A. J. Henderson (2008)
J. Immunol. 180, 1670-1677
   Abstract »    Full Text »    PDF »
MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression.
D. Y. Lee, Z. Deng, C.-H. Wang, and B. B. Yang (2007)
PNAS 104, 20350-20355
   Abstract »    Full Text »    PDF »
Analysis of the Interaction of Primate Retroviruses with the Human RNA Interference Machinery.
J. Lin and B. R. Cullen (2007)
J. Virol. 81, 12218-12226
   Abstract »    Full Text »    PDF »
Dicer is involved in protection against influenza A virus infection.
A. A. Matskevich and K. Moelling (2007)
J. Gen. Virol. 88, 2627-2635
   Abstract »    Full Text »    PDF »
RISCy Business: MicroRNAs, Pathogenesis, and Viruses.
B. Berkhout and K.-T. Jeang (2007)
J. Biol. Chem. 282, 26641-26645
   Full Text »    PDF »
Rapid transit in the immune cells: the role of mRNA turnover regulation.
K. S. A. Khabar (2007)
J. Leukoc. Biol. 81, 1335-1344
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882