Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-11-21
pubmed:abstractText
HIV-1 Nef incorporates into virions at low levels, likely about 10 molecules per viral particle. Here, we describe a Nef mutant (Nef7) apparently showing more than 100-fold higher efficiency of virion incorporation. Interestingly, Nef7 can act as a cargo molecule for protein delivery into the cells, as its virion incorporation appeared conserved even upon C-terminal fusion with proteins of up to 30 kDa. This was demonstrated first by assessing the intracellular fluorescence of cells challenged with lentivirus-based virus-like particles (VLPs) pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G) and incorporating Nef7 fused with the green fluorescent protein. Furthermore, the biologic activity of products delivered by Nef7-based VLPs was demonstrated by tagging Nef7 with the herpes simplex virus-1 thymidine kinase (HSV-1 TK). In fact, we observed that both cell lines and primary human macrophages challenged with (VSV-G) Nef7/TK VLPs died after 5 to 7 days of treatment with ganciclovir (GCV). In sum, our findings support the notion that Nef7-based VLPs can be considered platforms for original systems of protein delivery. In particular, the here- described Nef7/TK VLPs represent a first applicative example opening the way toward new HSV-1 TK/GCV-based cell suicide therapies circumventing cell gene engineering procedures.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1525-0016
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1185-96
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16095973-Blotting, Western, pubmed-meshheading:16095973-Cell Line, pubmed-meshheading:16095973-Detergents, pubmed-meshheading:16095973-Ganciclovir, pubmed-meshheading:16095973-Gene Therapy, pubmed-meshheading:16095973-Gene Transfer Techniques, pubmed-meshheading:16095973-Green Fluorescent Proteins, pubmed-meshheading:16095973-HIV-1, pubmed-meshheading:16095973-Herpesvirus 1, Human, pubmed-meshheading:16095973-Humans, pubmed-meshheading:16095973-Kinetics, pubmed-meshheading:16095973-Lentivirus, pubmed-meshheading:16095973-Macrophages, pubmed-meshheading:16095973-Membrane Glycoproteins, pubmed-meshheading:16095973-Membrane Microdomains, pubmed-meshheading:16095973-Models, Genetic, pubmed-meshheading:16095973-Protein Structure, Tertiary, pubmed-meshheading:16095973-Recombinant Fusion Proteins, pubmed-meshheading:16095973-Retroviridae, pubmed-meshheading:16095973-Thymidine Kinase, pubmed-meshheading:16095973-Time Factors, pubmed-meshheading:16095973-Viral Envelope Proteins
pubmed:year
2005
pubmed:articleTitle
Cell death induced by the herpes simplex virus-1 thymidine kinase delivered by human immunodeficiency virus-1-based virus-like particles.
pubmed:affiliation
Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't