Downregulation of HIV-1 vif by a hammerhead ribozyme expressed from a retroviral vector.(Clinical report): An article from: Journal of the South Carolina Academy of Science

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From the author: HIV infection of CD4+ T helper cells results in a gradual deterioration of immune function and leads to the onset of the Acquired Immune Deficiency Syndrome (AIDS). Current research suggests that HIV infection may be combated with ribozyme therapy. Hammerhead ribozymes are small, catalytic RNAs that can be designed to cleave substrate RNAs at specific sequences, and those targeted to HIV-1 mRNAs have been shown to greatly reduce or inhibit viral replication. The HIV-1 virion infectivity factor (vif) gene encodes a protein that counteracts an innate, antiretroviral defense mechanism of nonpermissive CD4+ T helper cells. This mechanism is mediated by apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G), a cellular cytidine deaminase that is encapsulated into assembling virions in the absence of vif and is inhibitory during the next round of viral replication. Vif neutralizes APOBEC3G by reducing its translation and by rapid degradation of the native protein. Vif mRNA, therefore, may be a good target for ribozyme mediated inhibition of HIV-1 replication. To test this hypothesis a catalytic hammerhead ribozyme targeted to nucleotide 5113 of the HIV-1 genomic clone NL43 (Accession # M19221) was designed and synthesized. A non-catalytic control, Vif5113A was also designed and synthesized. Vif5113 and Vif5113A were cloned into the retroviral vector, pSuper.retro.puro (pSRP) to facilitate tissue culture studies. In this study, Vif5113 and Vif113A ribozymes were analyzed for their ability to reduce vif expression in an intracellular cleavage assay. These studies, as determined by Western blot analysis, suggested that vif expression was reduced in the presence of the catalytic ribozyme Vif5113.

Citation Details
Title: Downregulation of HIV-1 vif by a hammerhead ribozyme expressed from a retroviral vector.(Clinical report)
Author: Audrey M. Hendley
Publication:Journal of the South Carolina Academy of Science (Magazine/Journal)
Date: September 22, 2009
Publisher: South Carolina Academy of Science
Volume: 7 Issue: 2 Page: 14(4)

Article Type: Clinical report

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