Selective packaging of cellular miRNAs in HIV-1 particles.

Retroviral particles are known to package specific host cell components such as RNA molecules in addition to the two copies of the viral RNA genome. The highly sensitive SOLiD sequencing technology was used to determine the cellular miRNA content of human immunodeficiency virus type 1 (HIV-1) particles. We determined the relative concentration of cellular miRNAs in a T cell line and several primary cell subsets before and after HIV-1 infection, and compared those values to the miRNA content of virion particles.

Deep sequencing of virus-infected cells reveals HIV-encoded small RNAs.

Small virus-derived interfering RNAs (viRNAs) play an important role in antiviral defence in plants, insects and nematodes by triggering the RNA interference (RNAi) pathway. The role of RNAi as an antiviral defence mechanism in mammalian cells has been obscure due to the lack of viRNA detection. Although viRNAs from different mammalian viruses have recently been identified, their functions and possible impact on viral replication remain unknown.

RNAi and cellular miRNAs in infections by mammalian viruses.

MicroRNAs (miRNAs) play an essential role in the regulation of eukaryotic gene expression. Recent studies demonstrate that miRNAs can also strongly affect the replication of pathogenic viruses. For example, cellular miRNAs can target and repress the expression of viral mRNAs, but there is also at least one example of a cellular miRNA that stimulates virus replication.

Calorimetric investigation of triazole-bridged Fe(II) spin-crossover one-dimensional materials: measuring the cooperativity.

The relevance of abrupt magnetic and optical transitions exhibiting bistability in spin-crossover solids has been pointed out for their potential applications in optical or memory devices. In this respect, triazole-based one-dimensional coordination polymers are widely recognized as one of the most interesting systems. The measure of the interaction among spin-crossover centers at the origin of such cooperative behavior is of paramount importance and has so far been realized through modeling of spin-crossover curves derived mostly from magnetic measurements.

A miRNA-tRNA mix-up: tRNA origin of proposed miRNA.

The rapid release of new data from DNA genome sequencing projects has led to a variety of misannotations in public databases. Our results suggest that next generation sequencing approaches are particularly prone to such misannotations. Two related miRNA candidates did recently enter the miRBase database, miR-1274b and miR-1274a, but they share identical 18-nucleotide stretches with tRNA (Lys3) and tRNA (Lys5) , respectively.

Combinatorial RNAi against HIV-1 using extended short hairpin RNAs.

RNA interference (RNAi) is a widely used gene suppression tool that holds great promise as a novel antiviral approach. However, for error-prone viruses including human immunodeficiency virus type 1(HIV-1), a combinatorial approach against multiple conserved sequences is required to prevent the emergence of RNAi-resistant escape viruses. Previously, we constructed extended short hairpin RNAs (e-shRNAs) that encode two potent small interfering RNAs (siRNAs) (e2-shRNAs).

RNAi-mediated inhibition of HIV-1 by targeting partially complementary viral sequences.

Potent antiviral RNAi can be induced by intracellular expression of short hairpin RNAs (shRNAs) and artificial microRNAs (miRNAs). Expression of shRNA and miRNA results in target mRNA degradation (perfect base pairing) or translational repression (partial base pairing). Although efficient inhibition can be obtained, error-prone viruses such as human immunodeficiency virus type 1 (HIV-1) can escape from RNAi-mediated inhibition by mutating the target sequence.

Differential RNA silencing suppression activity of NS1 proteins from different influenza A virus strains.

The NS1 gene of influenza A virus encodes a multi-functional protein that plays an important role in counteracting cellular antiviral mechanisms such as the interferon (IFN), protein kinase R and retinoic acid-inducible gene product I pathways. In addition, NS1 has recently been shown to have RNA interference (RNAi) or RNA silencing suppression (RSS) activity. This study analysed the IFN antagonistic activity of NS1 and the RSS activity for several influenza subtypes: H1N1, H3N2, H5N1 and H7N7.

The NS3 protein of rice hoja blanca virus complements the RNAi suppressor function of HIV-1 Tat.

The question of whether RNA interference (RNAi) acts as an antiviral mechanism in mammalian cells remains controversial. The antiviral interferon (IFN) response cannot easily be distinguished from a possible antiviral RNAi pathway owing to the involvement of double-stranded RNA (dsRNA) as a common inducer molecule. The non-structural protein 3 (NS3) protein of rice hoja blanca virus (RHBV) is an RNA silencing suppressor (RSS) that exclusively binds to small dsRNA molecules.

Nucleic acids-based therapeutics in the battle against pathogenic viruses.

For almost three decades, researchers have studied the possibility to use nucleic acids as antiviral therapeutics. In theory, compounds such as antisense oligonucleotides, ribozymes, DNAzymes, and aptamers can be designed to trigger the sequence-specific inhibition of particular mRNA transcripts, including viral genomes. However, difficulties with their efficiency, off-target effects, toxicity, delivery, and stability halted the development of nucleic acid-based therapeutics that can be used in the clinic.

Counterion effect on the spin-transition properties of the cation [Fe(btzx)3]2+ (btzx=m-Xylylenebis(tetrazole)).

The influence of the counteranion on the structure and the spin-transition properties of original 1D bis(tetrazole) Fe(II) systems, namely [Fe(btzx)(3)]X(2) (X=PF(6) (-) (1), CF(3)SO(3) (-) (2) and ClO(4) (-) (3); btzx=m-xylylenebis(tetrazole)) is studied. The X-ray crystal structures of compounds 1 and 2 are described in detail. These structures present a solvent molecule encapsulated within pockets formed by btzx ligands along the 1D coordination chains.

Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA polycistron.

RNA interference (RNAi) is a powerful approach to inhibit human immunodeficiency virus type 1 (HIV-1) replication. However, HIV-1 can escape from RNAi-mediated antiviral therapy by selection of mutations in the targeted sequence. To prevent viral escape, multiple small interfering RNAs (siRNAs) against conserved viral sequences should be combined.

Increased virus replication in mammalian cells by blocking intracellular innate defense responses.

The mammalian innate immune system senses viral infection by recognizing viral signatures and activates potent antiviral responses. Besides the interferon (IFN) response, there is accumulating evidence that RNA silencing or RNA interference (RNAi) serves as an antiviral mechanism in mammalian cells. Mammalian viruses encode IFN antagonists to counteract the IFN response in infected cells.

RNA interference against viruses: strike and counterstrike.

RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA. RNAi holds great promise as a novel nucleic acid-based therapeutic against a wide variety of diseases, including cancer, infectious diseases and genetic disorders. Antiviral RNAi strategies have received much attention and several compounds are currently being tested in clinical trials.

[Fe(mu-btzmp)2(btzmp)2](ClO4)2: a doubly-bridged 1D spin-transition bistetrazole-based polymer showing thermal hysteresis behaviour.

The reaction of btzmp (1,2-bis(tetrazol-1-yl)-2-methylpropane) with Fe(ClO4)2 generates a 1D polymeric species, [Fe(mu-btzmp)2(btzmp)2](ClO4)2, showing a steep spin transition (T(1/2) / =136 K and T(1/2) / =133 K) with a 3 K thermal hysteresis. The crystal structure at 100 and 200 K reveals that, in contrast to other bistetrazole based spin-transition systems such as [Fe(endi)3](BF4)2 and [Fe(btzp)3](ClO4)2, the present compound has only two ligands bridging the metallic centres, while the other two coordination positions are occupied by two mono-coordinated (non-bridging) btzmp ligands. This peculiarity confers an unprecedented crystal packing in the series of 1D bistetrazole based polymers.

Design of extended short hairpin RNAs for HIV-1 inhibition.

RNA interference (RNAi) targeted towards viral mRNAs is widely used to block virus replication in mammalian cells. The specific antiviral RNAi response can be induced via transfection of synthetic small interfering RNAs (siRNAs) or via intracellular expression of short hairpin RNAs (shRNAs). For HIV-1, both approaches resulted in profound inhibition of virus replication.

The Ebola virus VP35 protein is a suppressor of RNA silencing.

RNA silencing or interference (RNAi) is a gene regulation mechanism in eukaryotes that controls cell differentiation and developmental processes via expression of microRNAs. RNAi also serves as an innate antiviral defence response in plants, nematodes, and insects. This antiviral response is triggered by virus-specific double-stranded RNA molecules (dsRNAs) that are produced during infection.

Efficient inhibition of HIV-1 expression by LNA modified antisense oligonucleotides and DNAzymes targeted to functionally selected binding sites.

Background: A primary concern when targeting HIV-1 RNA by means of antisense related technologies is the accessibility of the targets. Using a library selection approach to define the most accessible sites for 20-mer oligonucleotides annealing within the highly structured 5'-UTR of the HIV-1 genome we have shown that there are at least four optimal targets available.

Results: The biological effect of antisense DNA and LNA oligonucleotides, DNA- and LNAzymes targeted to the four most accessible sites was tested for their abilities to block reverse transcription and dimerization of the HIV-1 RNA template in vitro, and to suppress HIV-1 production in cell culture.

Trans-inhibition of HIV-1 by a long hairpin RNA expressed within the viral genome.

Background: Human immunodeficiency virus type 1 (HIV-1) can be inhibited by means of RNA silencing or interference (RNAi) using synthetic short interfering RNAs (siRNAs) or gene constructs encoding short hairpin RNAs (shRNAs) or long hairpin RNAs (lhRNAs). The use of siRNA and shRNA as antiviral therapeutic is limited because of the emergence of viral escape mutants. This problem is theoretically prevented by intracellular expression of lhRNAs generating multiple siRNAs that target the virus simultaneously, thus reducing the chance of viral escape.

Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA.

Inhibition of virus replication by means of RNA interference has been reported for several important human pathogens, including human immunodeficiency virus type 1 (HIV-1). RNA interference against these pathogens has been accomplished by introduction of virus-specific synthetic small interfering RNAs (siRNAs) or DNA constructs encoding short-hairpin RNAs (shRNAs). Their use as therapeutic antiviral against HIV-1 is limited, because of the emergence of viral escape mutants.

RNA interference: its use as antiviral therapy.

RNA interference (RNAi) is a sequence-specific gene-silencing mechanism that has been proposed to function as a defence mechanism of eukaryotic cells against viruses and transposons. RNAi was first observed in plants in the form of a mysterious immune response to viral pathogens. But RNAi is more than just a response to exogenous genetic material.

The interplay between virus infection and the cellular RNA interference machinery.

RNA interference (RNAi) plays a pivotal role in the regulation of gene expression to control cell development and differentiation. In plants, insects and nematodes RNAi also functions as an innate defence response against viruses. Similarly, there is accumulating evidence that RNAi functions as an antiviral defence mechanism in mammalian cells.

Low-spin state structure of [Fe(chloroethyltetrazole)6](BF4)2 obtained from synchrotron powder diffraction data.

The complex [Fe(teec)6](BF4)2 (teec = chloroethyltetrazole) shows a two-step complete spin-crossover transition in the temperature range 300-90 K. Time-resolved synchrotron powder diffraction experiments have been carried out in this temperature range, and crystal structure models have been obtained from the powder patterns by using the parallel tempering technique. Of these models, the low-spin state structure at 90 K has been refined completely with Rietveld refinement.