A neuron-specific gene transfer by a recombinant defective Sindbis virus

Gwag, Byoung Joo; Kim, Eun Y.; Ryu, Bo Rum; Won, Seok Joon; Ko, Hyuk Wan; Oh, Young J.; Cho, Young Gyu; Ha, Sang‐Jun; Sung, Young Chul

doi:10.1016/s0169-328x(98)00251-4

Cited by 37 publications

(40 citation statements)

References 42 publications

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“…However, these treatments have no effects on RRV binding, suggesting that, unlike Sindbis virus, RRV virus does not utilize heparan sulfate as a cellular receptor (8). This difference in the use of cellular receptors may explain in part the discrepancy in the cellular tropism in the central nervous system between RRVpseudotyped FIV vector and Sindbis virus/Semliki Forest vi- (21). In contrast, our results suggest that the FIV pseudotyped with RRV envelope glycoproteins preferentially transduces neuroglia.…”

Section: Discussionmentioning

confidence: 58%

In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins

Kang

Stein²,

Heth³

et al. 2002

J Virol

126

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Vectors derived from lentiviruses provide a promising gene delivery system. We examined the in vivo gene transfer efficiency and tissue or cell tropism of a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the glycoproteins from Ross River Virus (RRV). RRV glycoproteins were efficiently incorporated into FIV virions, generating preparations of FIV vector, which after concentration attain titers up to 1.5 ؋ 10 8 TU/ml. After systemic administration, RRV-pseudotyped FIV vectors (RRV/FIV) predominantly transduced the liver of recipient mice. Transduction efficiency in the liver with the RRV/FIV was ca. 20-fold higher than that achieved with the vesicular stomatitis virus G protein (VSV-G) pseudotype. Moreover, in comparison to VSV-G, the RRV glycoproteins caused less cytotoxicity, as determined from the levels of glutamic pyruvic transaminase and glutamic oxalacetic transaminase in serum. Although hepatocytes were the main liver cell type transduced, nonhepatocytes (mainly Kupffer cells) were also transduced. The percentages of the transduced nonhepatocytes were comparable between RRV and VSV-G pseudotypes and did not correlate with the production of antibody against the transgene product. After injection into brain, RRV/FIV preferentially transduced neuroglial cells (astrocytes and oligodendrocytes). In contrast to the VSV-G protein that targets predominantly neurons, <10% of the brain cells transduced with the RRV pseudotyped vector were neurons. Finally, the gene transfer efficiencies of RRV/FIV after direct application to skeletal muscle or airway were also examined and, although transgene-expressing cells were detected, their proportions were low. Our data support the utility of RRV glycoprotein-pseudotyped FIV lentiviral vectors for hepatocyte-and neurogliarelated disease applications.

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Section: Discussionmentioning

confidence: 58%

In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins

Kang

Stein²,

Heth³

et al. 2002

J Virol

126

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“…Homer 1a, a dominant negative subtype, is expressed at high levels after neuronal insult or stress and less severe activity such as that during novel experience (5). To assess its role in regulating mGluR5 coupling to effectors at the postsynapse, Homer 1a was expressed in autapses by using the Sindbis viral expression system (28)(29)(30). Fig.…”

Section: Resultsmentioning

confidence: 99%

Homer 1a uncouples metabotropic glutamate receptor 5 from postsynaptic effectors

Kammermeier

Worley²

2007

Proc. Natl. Acad. Sci. U.S.A.

114

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Metabotropic glutamate receptors (mGluRs) and Homer proteins play critical roles in neuronal functions including plasticity, nociception, epilepsy, and drug addiction. Furthermore, Homer proteins regulate mGluR1/5 function by acting as adapters and facilitating coupling to effectors such as the inositol triphosphate receptor. However, although Homer proteins and their interaction with mGluRs have been the subject of intense study, direct measurements of Homer-induced changes in postsynaptic mGluReffector coupling have not been reported. This question was addressed here by examining glutamatergic excitatory postsynaptic currents (EPSCs) in rat autaptic hippocampal cultures. In most neurons, the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine strongly inhibited the EPSC acutely. This modulation occurred postsynaptically, was mediated primarily by mGluR5, and was inositol triphosphate receptor-dependent. Expression of the dominant negative, immediate early form of Homer, Homer 1a, strongly reduced EPSC modulation, but the W24A mutant of Homer 1a, which cannot bind mGluRs, had no effect. (S)-3,5-dihydroxyphenylglycine-mediated intracellular calcium responses in the processes of Homer 1a-expressing neurons were reduced compared with those in Homer 1a W24A-expressing cells. However, neither the distribution of mGluR5 nor the modulation of somatic calcium channels was altered by Homer 1a expression. These data demonstrate that Homer 1a can reduce mGluR5 coupling to postsynaptic effectors without relying on large changes in the subcellular distribution of the receptor. Thus, alteration of mGluR signaling by changes in Homer protein expression may represent a viable mechanism for fine-tuning synaptic strength in neurons.autapse ͉ calcium channel ͉ excitatory postsynaptic current ͉ hippocampal M etabotropic glutamate receptors (mGluRs) are class 3 G protein-coupled receptors expressed throughout the brain. Group I mGluRs 1 and 5 couple to the phospholipase C/calcium release cascade and to pathways regulating ion channels and synaptic currents (1, 2). In the brain, group I mGluRs are often expressed postsynaptically, where they regulate NMDA and AMPA receptor function and mediate multiple forms of plasticity (3).The Homer family of postsynaptic scaffolding proteins was discovered by the regulated expression of the member subsequently termed Homer 1a (4). Levels of Homer 1a and variant Ania-3 are increased after periods of activity or stress, injury, or novel experience (4, 5). Other ''long'' Homer proteins (1b, 1c, 2, and 3) are expressed constitutively (6-8) and, unlike Homer 1a, form clusters mediated by their long C termini. Homer proteins organize postsynaptic proteins around the active site (7) by binding several targets including group I mGluRs, inositol triphosphate receptors (IP 3 Rs), Shank, and the TRPC1 cation channel (9-12).Homer proteins also influence the function of their binding partners. Binding to Homers can alter the function of TRPC1 (12), and group I mGluRs couple more strongly to some effectors (...

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“…In brain slices, foreign genes, including GFP, have been introduced by using biolistic gene transfer (Lo et al 1994) and viral transfection by using adenovirus (Moriyoshi et al 1996), vaccinia virus (Pettit et al 1995), and Sindbis virus ). It has also been shown that adenovirus (Moriyoshi et al 1996) and Sindbis (Gwag et al 1998) vectors can be used for gene transfer in neocortex in vivo. We use a replication-defective, neurotropic, recombinant Sindbis virus (SIN-EGFP) (Corsini et al 1996) that was engineered to express enhanced GFP (EGFP) (Corsini et al 1996;Maletic-Savatic et al 1999;Malinow et al 2000;Lendvai et al 2000).…”

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confidence: 99%

Imaging High-Resolution Structure of GFP-Expressing Neurons in Neocortex In Vivo

Chen¹,

Lendvai²,

Nimchinsky³

et al. 2000

Learn. Mem.

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To detect subtle changes in neuronal morphology in response to changes in experience, one must image neurons at high resolution in vivo over time scales of minutes to days. We accomplished this by infecting postmitotic neurons in rat and mouse barrel cortex with a Sindbis virus carrying the gene for enhanced green fluorescent protein. Visualized with 2-photon excitation laser scanning microscopy, infected neurons showed bright fluorescence that was distributed homogeneously throughout the cell, including axonal and dendritic arbors. Single dendritic spines could routinely be resolved and their morphological dynamics visualized. Viral infection and imaging were achieved throughout postnatal development up to early adulthood (P 8-30), although the viral efficiency of infection decreased with age. This relatively noninvasive method for fluorescent labeling and imaging of neurons allows the study of morphological dynamics of neocortical neurons and their circuits in vivo.

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A neuron-specific gene transfer by a recombinant defective Sindbis virus

Cited by 37 publications

References 42 publications

In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins

In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins

Homer 1a uncouples metabotropic glutamate receptor 5 from postsynaptic effectors

Imaging High-Resolution Structure of GFP-Expressing Neurons in Neocortex In Vivo

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