HIVsirDB: A Database of HIV Inhibiting siRNAs

Background Human immunodeficiency virus (HIV) is responsible for millions of deaths every year. The current treatment involves the use of multiple antiretroviral agents that may harm patients due to their toxic nature. RNA interference (RNAi) is a potent candidate for the future treatment of HIV, uses short interfering RNA (siRNA/shRNA) for silencing HIV genes. In this study, attempts have been made to create a database HIVsirDB of siRNAs responsible for silencing HIV genes. Descriptions HIVsirDB is a manually curated database of HIV inhibiting siRNAs that provides comprehensive information about each siRNA or shRNA. Information was collected and compiled from literature and public resources. This database contains around 750 siRNAs that includes 75 partially complementary siRNAs differing by one or more bases with the target sites and over 100 escape mutant sequences. HIVsirDB structure contains sixteen fields including siRNA sequence, HIV strain, targeted genome region, efficacy and conservation of target sequences. In order to facilitate user, many tools have been integrated in this database that includes; i) siRNAmap for mapping siRNAs on target sequence, ii) HIVsirblast for BLAST search against database, iii) siRNAalign for aligning siRNAs. Conclusion HIVsirDB is a freely accessible database of siRNAs which can silence or degrade HIV genes. It covers 26 types of HIV strains and 28 cell types. This database will be very useful for developing models for predicting efficacy of HIV inhibiting siRNAs. In summary this is a useful resource for researchers working in the field of siRNA based HIV therapy. HIVsirDB database is accessible at http://crdd.osdd.net/raghava/hivsir/.

[1]  N. Yamamoto,et al.  Inhibition of HIV-1 replication by long-term treatment with a chimeric RNA containing shRNA and TAR decoy RNA. , 2009, Antiviral research.

[2]  K. Crandall,et al.  The causes and consequences of HIV evolution , 2004, Nature Reviews Genetics.

[3]  Sunit K. Singh,et al.  siRNAs: their potential as therapeutic agents--Part I. Designing of siRNAs. , 2009, Drug discovery today.

[4]  T. Applegate,et al.  Multiple shRNA combinations for near-complete coverage of all HIV-1 strains , 2011, AIDS research and therapy.

[5]  B. Berkhout,et al.  Trans-inhibition of HIV-1 by a long hairpin RNA expressed within the viral genome , 2007 .

[6]  J. Rossi.  RNAi as a treatment for HIV-1 infection. , 2006, BioTechniques.

[7]  Ben Berkhout,et al.  HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome , 2005, Nucleic acids research.

[8]  A. Jaramillo,et al.  96 shRNAs designed for maximal coverage of HIV-1 variants , 2009, Retrovirology.

[9]  Yuki Naito,et al.  Optimal design and validation of antiviral siRNA for targeting HIV-1 , 2007, Retrovirology.

[10]  J. Chermann,et al.  Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). , 1983, Science.

[11]  Erik L. L. Sonnhammer,et al.  siRNAdb: a database of siRNA sequences , 2004, Nucleic Acids Res..

[12]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[13]  D. Weissman,et al.  Inhibition of HIV-1 Infection by Small Interfering RNA-Mediated RNA Interference1 , 2002, The Journal of Immunology.

[14]  J. Chermann,et al.  Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). 1983. , 2004, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[15]  L. Montagnier.  25 years after HIV discovery: prospects for cure and vaccine. , 2010, Virology.

[16]  Ben Berkhout,et al.  Lentiviral Vector Design for Multiple shRNA Expression and Durable HIV-1 Inhibition , 2008, Molecular Therapy.

[17]  L. I. B. Kanzaki,et al.  RNA interference and HIV‐1 infection , 2008, Reviews in medical virology.

[18]  M. Robb.  Failure of the Merck HIV vaccine: an uncertain step forward , 2008, The Lancet.

[19]  J. Mcghee,et al.  HIV infection: first battle decides the war. , 2006, Trends in immunology.

[20]  J. Lieberman,et al.  Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIV. , 2005, Blood.

[21]  E. Sontheimer,et al.  Origins and Mechanisms of miRNAs and siRNAs , 2009, Cell.

[22]  Sunit K. Singh.  RNA interference and its therapeutic potential against HIV infection. , 2008, Expert opinion on biological therapy.

[23]  A. Nicoll,et al.  The public health significance of HIV-1 subtypes , 2001, AIDS.

[24]  B. Clotet,et al.  Sequence Homology Required by Human Immunodeficiency Virus Type 1 To Escape from Short Interfering RNAs , 2006, Journal of Virology.

[25]  B. Ramratnam,et al.  Human Immunodeficiency Virus Type 1 Escape from RNA Interference , 2003, Journal of Virology.

[26]  Jean-Yves Nau,et al.  [A new human immunodeficiency virus derived from gorillas]. , 2009, Revue medicale suisse.

[27]  Tongbin Li,et al.  siRecords: a database of mammalian RNAi experiments and efficacies , 2008, Nucleic Acids Res..

[28]  Szymon M. Kielbasa,et al.  HuSiDa—the human siRNA database: an open-access database for published functional siRNA sequences and technical details of efficient transfer into recipient cells , 2004, Nucleic Acids Res..

[29]  J Leibowitch,et al.  Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). , 1983, Science.

[30]  J. Lieberman,et al.  siRNA-directed inhibition of HIV-1 infection , 2002, Nature Medicine.

[31]  B. Berkhout,et al.  Long-term inhibition of HIV-1 replication with RNA interference against cellular co-factors. , 2011, Antiviral research.

[32]  A. Reynolds,et al.  Rational siRNA design for RNA interference , 2004, Nature Biotechnology.

[33]  Ali Ehsani,et al.  Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells , 2002, Nature Biotechnology.

[34]  M. Stevenson,et al.  Modulation of HIV-1 replication by RNA interference , 2002, Nature.

[35]  B. Berkhout,et al.  A novel approach for inhibition of HIV-1 by RNA interference: counteracting viral escape with a second generation of siRNAs , 2005, Journal of RNAi and gene silencing : an international journal of RNA and gene targeting research.

[36]  Kyle A. McQuisten,et al.  Comparing Artificial Neural Networks, General Linear Models and Support Vector Machines in Building Predictive Models for Small Interfering RNAs , 2009, PloS one.

[37]  Dieter Huesken,et al.  Design of a genome-wide siRNA library using an artificial neural network , 2005, Nature Biotechnology.

[38]  Lung-Ji Chang,et al.  Lentiviral siRNAs targeting multiple highly conserved RNA sequences of human immunodeficiency virus type 1 , 2005, Gene Therapy.