Pseudotyping Lentiviral Vectors with Aura Virus Envelope Glycoproteins for DC-SIGN–Mediated Transduction of Dendritic Cells

Froelich, Steven; Tai, April; Kennedy, Kathleen E.; Zubair, Adnan; Wang, Pin

doi:10.1089/hum.2010.196

Cited by 12 publications

(8 citation statements)

References 50 publications

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“…Previous work by others has established that LV vectors can be pseudotyped with the envelope proteins of other alphaviruses such as Ross River virus (RRV), [23][24][25] Sindbis virus, 26 Western equine encephalitis virus, 27 Semliki Forest virus 28 and most recently AURA virus. 29 Although these envelopes constituted valuable components to efficiently alter the tropism of LVs, to date, only RRV LV vectors have reported high enough titres to allow transgene expression to be examined in vivo. 23,30 Here, we show that VEEV-G-pseudotyped LVs can be produced at high titres, and these vectors mediate stable and efficient in vivo transgene delivery.…”

Section: Discussionmentioning

confidence: 99%

Venezuelan equine encephalitis virus glycoprotein pseudotyping confers neurotropism to lentiviral vectors

et al. 2012

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We have produced high-titre HIV-1 green fluorescent protein-expressing lentiviral (LV) vectors pseudotyped with strain 3908 Venezuelan equine encephalitis virus glycoprotein (VEEV-G) and used them to study transduction of: (1) rat embryonic motor neuron (MN) and striatal neuron primary cultures, (2) differentiated MN cell line NSC-34 and (3) adult rat striatum. In primary neuronal cultures, transduction with VEEV-G-pseudotyped LV was more efficient and more neuronal than with vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped LV. In NSC-34 cells clear retrograde transport of VEEV-G vector particles was observed. In the striatum at the injection site, transduction with the VEEV-G vectors driven by cytomegalovirus or phosphoglycerate kinase promoters exhibited a distinct neuronal tropism with no microglial and only a minor astroglial component, superior to that obtained with VSV-G-pseudotyped LV, irrespective of the promoter used. Neuronal transduction efficiency increased over time. Distal to the injection site transduction of mitral cells in the olfactory bulb, thalamic neurons and dopaminergic neurons in the substantia nigra pars compacta was detected. This, together with observations of retrograde axonal trafficking in vitro indicates that these vectors also possess low level of retrograde neuronal transduction capability in vivo. In this study, we demonstrate both strong neurotropism as well as sustainability of expression and minimal host immune response in vivo, making the VEEV-G-pseudotyped LV vectors potentially useful for gene therapy of neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Venezuelan equine encephalitis virus glycoprotein pseudotyping confers neurotropism to lentiviral vectors

et al. 2012

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“…C-type lectins, including dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and liver-specific SIGN (L-SIGN), can act as an attachment factors for some alphaviruses [ 67 , 68 ]. In addition to their role in cell migration [ 69 ], these proteins function as pattern recognition receptors (PRRs) by binding high-mannose N-glycans on the surface of pathogens [ 70 ].…”

Section: Attachment Factorsmentioning

confidence: 99%

A molecular understanding of alphavirus entry

et al. 2020

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Alphaviruses cause severe human illnesses including persistent arthritis and fatal encephalitis. As alphavirus entry into target cells is the first step in infection, intensive research efforts have focused on elucidating aspects of this pathway, including attachment, internalization, and fusion. Herein, we review recent developments in the molecular understanding of alphavirus entry both in vitro and in vivo and how these advances might enable the design of therapeutics targeting this critical step in the alphavirus life cycle.

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“…This argues against the notion that SINV-G is toxic to packaging cells (http://www.genetherapynet.com/viralvector/alphaviruses.html) which was not observed but favours stability issues postpackaging affecting titre. Milder methods of concentration, other than ultracentrifugation might overcome this problem and could also improve other alphaviral pseudotypes with low titres such as SFV [20], WEV [45] and AURA [46].…”

Section: Discussionmentioning

confidence: 99%

Selective transduction of astrocytic and neuronal CNS subpopulations by lentiviral vectors pseudotyped with Chikungunya virus envelope

et al. 2017

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NHAs was observed. In vivo stereotaxic delivery in striatum, thalamus and hippocampus respectively in the adult rat brain revealed localised transduction restricted to striatal astrocytes and hippocampal dentate granule neurons. Transduction of different subtypes of granule neurons from precursor to post-mitotic stages of differentiation was evident in the sub-granular zone and dentate granule cell layer. No significant inflammatory response was observed, but comparable to that of VSV-G pseudotyped lentiviral vectors. Robust longterm expression followed for three months post-transduction along with absence of neuroinflammation, coupled to the selective and unique neuron/glial tropism indicates that these vectors could be useful for modelling and gene therapy studies in the CNS.

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Pseudotyping Lentiviral Vectors with Aura Virus Envelope Glycoproteins for DC-SIGN–Mediated Transduction of Dendritic Cells

Cited by 12 publications

References 50 publications

Venezuelan equine encephalitis virus glycoprotein pseudotyping confers neurotropism to lentiviral vectors

Venezuelan equine encephalitis virus glycoprotein pseudotyping confers neurotropism to lentiviral vectors

A molecular understanding of alphavirus entry

Selective transduction of astrocytic and neuronal CNS subpopulations by lentiviral vectors pseudotyped with Chikungunya virus envelope

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