Liver-Specific Gene Therapy Using Lentiviral Vectors Based on Human Immunodeficiency Virus-1 (HIV-1)

2003 ◽  
Vol 104 (s49) ◽  
pp. 23P-23P
Author(s):  
Kathryn L Nash ◽  
Graeme J Alexander ◽  
Andrew M Lever
Keyword(s):  
Gene Therapy ◽  
Human Immunodeficiency Virus ◽  
Lentiviral Vectors ◽  
Specific Gene ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

scholarly journals A single administration of lentiviral vectors expressing either full-length human immunodeficiency virus 1 (HIV-1)HXB2 Rev/Env or codon-optimized HIV-1JR-FL gp120 generates durable immune responses in mice

2006 ◽  
Vol 87 (6) ◽  
pp. 1625-1634 ◽  
Author(s):  
Viviana Buffa ◽  
Donatella R. M. Negri ◽  
Pasqualina Leone ◽  
Roberta Bona ◽  
Martina Borghi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Viral Vectors ◽  
Lentiviral Vector ◽  
Lentiviral Vectors ◽  
Full Length ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Genetic immunization using viral vectors provides an effective means to elicit antigen-specific cellular immune responses. Several viral vectors have proven efficacious in inducing immune responses after direct injection in vivo. Among them, recombinant, self-inactivating lentiviral vectors are very attractive delivery systems, as they are able to efficiently transduce into and express foreign genes in a wide variety of mammalian cells. A self-inactivating lentiviral vector was evaluated for the delivery of human immunodeficiency virus 1 (HIV-1) envelope sequences in mice in order to elicit specific immune responses. With this aim, BALB/c mice were immunized with a single injection of self-inactivating lentiviral vectors carrying either the full-length HIV-1HXB2 Rev/Env (TY2-IIIBEnv) or the codon-optimized HIV-1JR-FL gp120 (TY2-JREnv) coding sequence. Both vectors were able to elicit specific cellular responses efficiently, as measured by gamma interferon ELISPOT and chromium-release assays, upon in vitro stimulation of splenocytes from BALB/c immunized mice. However, only the TY2-JREnv-immunized mice were able to elicit specific humoral responses, measured as anti-gp120 antibody production. These data provide the first evidence that a single, direct, in vivo administration of a lentiviral vector encoding a viral gene might represent a useful strategy for vaccine development.

scholarly journals APOBEC3H haplotypes and HIV-1 pro-viral vif DNA sequence diversity in early untreated human immunodeficiency virus–1 infection

2011 ◽  
Vol 72 (3) ◽  
pp. 207-212 ◽  
Author(s):  
P.A. Gourraud ◽  
A. Karaouni ◽  
J.M. Woo ◽  
T. Schmidt ◽  
J.R. Oksenberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Sequence ◽  
Sequence Diversity ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

scholarly journals Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation.

1989 ◽  
Vol 170 (5) ◽  
pp. 1681-1695 ◽  
Author(s):  
I Berkower ◽  
G E Smith ◽  
C Giri ◽  
D Murphy
Keyword(s):  
Genetic Diversity ◽  
Human Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Neutralizing Epitope ◽  
Vaccine Strategy ◽  
Disease Pathogenesis ◽  
Immunodeficiency Virus ◽  
High Degree ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

HIV-1 is known to show a high degree of genetic diversity, which may have major implications for disease pathogenesis and prevention. If every divergent isolate represented a distinct serotype, then effective vaccination might be impossible. However, using a sensitive new plaque-forming assay for HIV-1, we have found that most infected patients make neutralizing antibodies, predominantly to a group-specific epitope shared among three highly divergent isolates. This epitope persists among divergent isolates and rarely mutates, despite the rapid overall mutation rate of HIV-1, suggesting that it may participate in an essential viral function. These findings, plus the rarity of reinfections among these patients, suggest that HIV-1 may be more susceptible to a vaccine strategy based on a group-specific neutralizing epitope than was previously suspected.

scholarly journals Tat–Human Immunodeficiency Virus-1 Induces Human Monocyte Chemotaxis by Activation of Vascular Endothelial Growth Factor Receptor-1

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1365-1372 ◽  
Author(s):  
Stefania Mitola ◽  
Silvano Sozzani ◽  
Walter Luini ◽  
Luca Primo ◽  
Alessandro Borsatti ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Vascular Endothelial ◽  
Immunodeficiency Virus ◽  
Monocyte Chemotaxis ◽  
Endothelial Growth Factor ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addition, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus confirming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot analysis with an antibody anti–VEGFR-1/Flt-1 performed on monocyte phosphoproteins immunoprecipitated by an monoclonal antibody antiphosphotyrosine showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1.

Poly(ADP-ribose) polymerase inhibitors suppress UV-induced human immunodeficiency virus type 1 gene expression at the posttranscriptional level

1991 ◽  
Vol 11 (7) ◽  
pp. 3522-3527
Author(s):  
S Yamagoe ◽  
T Kohda ◽  
M Oishi
Keyword(s):  
Gene Expression ◽  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Specific Gene ◽  
Adp Ribosylation ◽  
Immunodeficiency Virus ◽  
Posttranscriptional Level ◽  
Hiv 1

Gene expression of human immunodeficiency virus type 1 (HIV-1) is induced not only by trans activation mediated through a gene product (tat) encoded by the virus but also by treatment of virus-carrying cells with DNA-damaging agents such as UV light. Employing an artificially constructed DNA in which the chloramphenicol acetyltransferase gene was placed under the control of the HIV-1 long terminal repeat, we analyzed the induction process in HeLa cells and found that inhibitors of poly(ADP-ribose) polymerase suppressed UV-induced HIV-1 gene expression but not tat-mediated expression. We also found that suppression occurs at the posttranscriptional level. These results indicate that HIV-1 gene expression is activated by at least two different mechanisms, one of which involves poly-ADP ribosylation. A possible new role of poly-ADP ribosylation in the regulation of specific gene expression is also discussed.

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