Sequence Homology Required by Human Immunodeficiency Virus Type 1 To Escape from Short Interfering RNAs

Sabariegos, Rosario; Giménez‐Barcons, Mireia; Tàpia, Natalia; Clotet, Bonaventura; Martı́nez, Miguel Ángel

doi:10.1128/jvi.80.2.571-577.2006

Cited by 74 publications

(59 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In these cases, the emergence of mutants was observed, either showing nucleotide substitutions or deletions within the targeted sequence (65), or evolving an alternative structure in its RNA genome occluding the siRNA binding site (66). A single substitution in the targeted sequence is sometimes sufficient to abolish the antiviral activity of siRNAs (67). Such problem may be circumvented by targeting the most conserved sequences at multiple locations in the HIV-1 genome (68).…”

Section: Small Rnas Directed Against Hiv-1mentioning

confidence: 99%

Emergence of a Complex Relationship between HIV-1 and the microRNA Pathway

Ouellet¹,

Plante²,

Barat³

et al. 2008

Methods in Molecular Biology

View full text Add to dashboard Cite

SummaryRecent experimental evidences support the existence of an increasingly complex and multifaceted interaction between viruses and the microRNA-guided RNA silencing machinery of human cells. The discovery of small interfering RNAs (siRNAs), which are designed to mediate cleavage of specific messenger RNAs (mRNAs), prompted virologists to establish therapeutic strategies based on siRNAs with the aim to suppress replication of several viruses, including human immunodeficiency virus type 1 (HIV-1). It has been appreciated only recently that viral RNAs can also be processed endogenously by the microRNA-generating enzyme Dicer or recognized by cellular miRNAs, in processes that could be viewed as an adapted antiviral defense mechanism. Known to repress mRNA translation through recognition of specific binding sites usually located in their 3′ untranslated region, miRNAs of host or viral origin may exert regulatory effects towards host and/or viral genes and influence viral replication and/or the host response to viral infection. This article summarizes our current state of knowledge on the relationship between HIV-1 and miRNA-guided RNA silencing, and discusses the different aspects of their interaction.

show abstract

Section: Small Rnas Directed Against Hiv-1mentioning

confidence: 99%

Emergence of a Complex Relationship between HIV-1 and the microRNA Pathway

Ouellet¹,

Plante²,

Barat³

et al. 2008

Methods in Molecular Biology

View full text Add to dashboard Cite

show abstract

“…It soon became apparent that HIV-1 is prone to viral escape in a mono-shRNA therapy [70][71][72][73][74][75][76][77][78], similar to single antiretroviral drug regimens. The therapeutic vector used in a clinical trial should therefore always tackle the virus with multiple inhibitors at the same time.…”

Section: Therapeutic Vector Designmentioning

confidence: 99%

RNA-interference-based Gene Therapy Approaches to HIV Type-1 Treatment: Tackling the Hurdles from Bench to Bedside

Eije

Berkhout

2009

Antivir Chem Chemother

View full text Add to dashboard Cite

RNA interference (RNAi) is a cellular mechanism that can be induced by small interfering RNAs (siRNAs) to mediate sequence-specific gene silencing by cleavage of the targeted messenger RNA. RNAi can be used as an antiviral approach to silence HIV type-1 (HIV-1) through stable expression of precursors, such as short hairpin RNAs (shRNAs), which are processed into siRNAs that can elicit degradation of HIV-1 RNAs. At the beginning of 2008, the first clinical trial using a lentivirus with an RNA-based gene therapy against HIV-1 was initiated. The antiviral molecules in this gene therapy consist of three RNA effectors, one of which triggers the RNAi pathway. This review article focuses on the basic principles of an RNAi-based gene therapy against HIV-1, including delivery methods, target selection, viral escape possibilities, systems for multiplexing siRNAs to achieve a durable therapy and the in vitro and in vivo test systems to evaluate the efficacy and safety of such a therapy.

show abstract

“…Insertion of shRNAs into a natural miRNA backbone has been shown to reduce such toxic effects (McBride et al, 2008). The high mutation rate of HIV-1 is an additional challenge in developing RNAi-based therapeutics, as a single point mutation within the targeted HIV-1 RNA sequence can abolish function of small RNAs and escape mutants emerge rapidly (Boden et al, 2003;Das et al, 2004;Sabariegos et al, 2006). This problem can be partly overcome by using a combination of small RNAs targeting several conserved regions of the viral genome and ideally expressed from a single therapeutic vector (ter Brake et al, 2006).…”

Section: Antiviral Rnasmentioning

confidence: 99%