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.

Originally published in Science Express on 22 February 2007
Science 16 March 2007:
Vol. 315. no. 5818, pp. 1579 - 1582
DOI: 10.1126/science.1136319
Prev | Table of Contents | Next

Reports

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*

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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 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 »
Transitioning Toward Evidence-Based Research in the Health Sciences for the XXI Century.
F. Chiappelli and O. S. Cajulis (2008)
Evid. Based Complement. Altern. Med. 5, 123-128
   Abstract »    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. ISSN 0036-8075 (print), 1095-9203 (online)