RNA silencing and HIV: A hypothesis for the etiology of the severe combined immunodeficiency induced by the virusReport as inadecuate




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Retrovirology

, 5:79

First Online: 11 September 2008Received: 27 February 2008Accepted: 11 September 2008

Abstract

A novel intrinsic HIV-1 antisense gene was previously described with RNA initiating from the region of an HIV-1 antisense initiator promoter element HIVaINR. The antisense RNA is exactly complementary to HIV-1 sense RNA and capable of forming ~400 base-pair bp duplex RNA in the region of the long terminal repeat LTR spanning the beginning portion of TAR in the repeat R region and extending through the U3 region. Duplex or double-stranded RNA of several hundred nucleotides in length is a key initiating element of RNA interference RNAi in several species. This HIVaINR antisense RNA is also capable of forming multiple stem-loop or hairpin-like secondary structures by M-fold analysis, with at least one that perfectly fits the criteria for a microRNA miRNA precursor. MicroRNAs miRNAs interact in a sequence-specific manner with target messenger RNAs mRNAs to induce either cleavage of the message or impede translation. Human mRNA targets of the predicted HIVaINR antisense RNA HAA microRNAs include mRNA for the human interleukin-2 receptor gamma chain IL-2RG, also called the common gamma γc receptor chain, because it is an integral part of 6 receptors mediating interleukin signalling IL-2R, IL-4R, IL-7R, IL-9R, IL-15R and IL-21R. Other potential human mRNA targets include interleukin-15 IL-15 mRNA, the fragile × mental retardation protein FMRP mRNA, and the IL-1 receptor-associated kinase 1 IRAK1 mRNA, amongst others. Thus the proposed intrinsic HIVaINR antisense RNA microRNAs HAAmiRNAs of the human immunodeficiency virus form complementary targets with mRNAs of a key human gene in adaptive immunity, the IL-2Rγc, in which genetic defects are known to cause an X-linked severe combined immunodeficiency syndrome X-SCID, as well as mRNAs of genes important in innate immunity. A new model of intrinsic RNA silencing induced by the HIVaINR antisense RNA in the absence of Tat is proposed, with elements suggestive of both small interfering RNA siRNA and miRNA.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-4690-5-79 contains supplementary material, which is available to authorized users.

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Author: Linda B Ludwig

Source: https://link.springer.com/



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