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© Research
Publication : Molecular therapy : the journal of the American Society of Gene Therapy

Production and neurotropism of lentivirus vectors pseudotyped with lyssavirus envelope glycoproteins

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular therapy : the journal of the American Society of Gene Therapy - 01 Aug 2001

Desmaris N, Bosch A, Salaün C, Petit C, Prévost MC, Tordo N, Perrin P, Schwartz O, de Rocquigny H, Heard JM

Link to Pubmed [PMID] – 11482987

Mol. Ther. 2001 Aug;4(2):149-56

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.

http://www.ncbi.nlm.nih.gov/pubmed/11482987