BASIC SCIENCE

Cell Research, 15(11-12):935-946, Nov-Dec 2005

siRNA, miRNA and HIV: promises and challenges

Man Lung YEUNG¹, Yamina BENNASSER¹, Shu Yun LE², Kuan Teh JEANG^1,*

¹Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland 20892-0460, USA
²Center for Cancer Research Nanobiology Program NCI Center for Cancer Research, NCI, National Institutes of Health, Fredrick, MD 21702, USA

Correspondence: Kuan Teh JEANG 301-496-6680 (phone) 301-480-3686 (fax) E-mail:kj7e@nih.gov Building 4, Room 306, 9000 Rockville Pike, Bethesda, MD 20892-0460, USA.

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Abstract

Small interfering RNA (siRNA) and microRNA (miRNA) are small RNAs of 18-25 nucleotides (nt) in length that play important roles in regulating gene expression. They are incorporated into an RNA-induced silencing complex (RISC) and serve as guides for silencing their corresponding target mRNAs based on complementary base-pairing. The promise of gene silencing has led many researchers to consider siRNA as an anti-viral tool. However, in long-term settings, many viruses appear to escape from this therapeutical strategy. An example of this may be seen in the case of human immunodeficiency virus type-1 (HIV-1) which is able to evade RNA silencing by either mutating the siRNA-targeted sequence or by encoding for a partial suppressor of RNAi (RNA interference). On the other hand, because miRNA targeting does not require absolute complementarity of base-pairing, mutational escape by viruses from miRNA-specified silencing may be more difficult to achieve. In this review, we discuss stratagems used by various viruses to avoid the cells' antiviral si/mi-RNA defenses and notions of how viruses might control and regulate host cell genes by encoding viral miRNAs (vmiRNAs).

Keywords: small interfering RNA, microRNA, RNA interference, human immunodeficiency virus type-1, RNA-induced silencing complex, suppressor of siRNA, viral miRNA.