Effective suppression of HIV-1 by artificial bispecific miRNA targeting conserved sequences with tolerance for wobble base-pairing
- Authors
- Son, Jiyeon; Uchil, Pradeep D.; Kim, Young Bong; Shankar, Premlata; Kumar, Priti; Lee, Sang-Kyung
- Issue Date
- Sep-2008
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- RNA interference; HIV; siRNA; shRNA; miRNA; conserved; lentivirus; wobble
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.374, no.2, pp.214 - 218
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 374
- Number
- 2
- Start Page
- 214
- End Page
- 218
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/171892
- DOI
- 10.1016/j.bbrc.2008.06.125
- ISSN
- 0006-291X
- Abstract
- The high genetic diversity and mutability of HIV pose a major problem for RNAi-mediated antiviral therapy. Simultaneous targeting of multiple highly conserved viral sequences has been suggested for durable cross-clade inhibition. Here we validate the approach of co-targeting two conserved sequences in the Tat and Vif genes. When coexpressed as artificial microRNA from a PoIII driven miR-155-based vector, the sequences together mediated effective and Sustained inhibition of HIV replication without virus break-out. To understand the nature of this efficient control, we analyzed genome sequences of 625 HIV-1 isolates in the Los Alamos Sequence database. Interestingly most natural variants were capable of wobble binding with the Tat/Vif siRNAs. Efficient silencing of reporter luciferase constructs bearing these variants residues verified that the Tat/Vif sequences together tolerated wobble binding and mediated functional RNAi. We propose the rationale of targeting highly conserved HIV sequences where wobble substitutions permit functional RNAi for global HIV repression.
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