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Production and neurotropism of lentivirus vectors pseudotyped with lyssavirus envelope glycoproteins.

Abstract : We investigated the production efficiency and the gene transfer capacity in the central nervous system of HIV-1-based vectors pseudotyped with either the G protein of the Mokola lyssaviruses (MK-G), a neurotropic virus causing rabies disease, or the vesiculo-stomatitis G protein (VSV-G). Both envelopes induced syncitia in cell cultures. They were incorporated into vector particles and mature virions were observed by electron microscopy. Vector production was two- to sixfold more efficient with VSV-G than with MK-G. For equivalent amounts of physical particles, vector titration was 5- to 25-fold higher with VSV-G than with MK-G pseudotypes on cultured cells, and in vivo gene expression in mouse brain was more intense. Thus, VSV-G pseudotypes were produced more efficiently and were more infectious than MK-G pseudotypes. Tropism for brain cells was analyzed by intrastriatal injections in rats. Both pseudotypes preferentially transduced neurons (70-90% of transduced cells). Retrograde axonal transport was investigated by instilling vector suspensions in the rat nasal cavity. Both pseudotypes were efficiently transported to olfactive neuron bodies. Thus, although coating HIV-1 particles with rabdhovirus envelope glycoproteins enables them to enter neuronal cells efficiently, pseudotyping is not sufficient to confer the powerful neurotropism of lyssaviruses to lentivirus vectors.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01372718
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Submitted on : Tuesday, September 27, 2016 - 3:42:52 PM
Last modification on : Thursday, May 28, 2020 - 1:50:06 PM

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Nathalie Desmaris, Assumpcio Bosch, Christine Salaün, Caroline Petit, Marie-Christine Prévost, et al.. Production and neurotropism of lentivirus vectors pseudotyped with lyssavirus envelope glycoproteins.. Molecular Therapy, Nature Publishing Group, 2001, 4 (2), pp.149-56. ⟨10.1006/mthe.2001.0431⟩. ⟨pasteur-01372718⟩

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