Gene Therapy Using a Simian Virus 40–Derived Vector Inhibits the Development of In Vivo Human Immunodeficiency Virus Type 1 Infection of Severe Combined Immunodeficiency Mice Implanted with Human Fetal Thymic and Liver Tissue

Goldstein, Harris; Pettoello-Mantovani, Massimo; Anderson, Christina M.; Cordelier, Pierre; Pomerantz, Roger J.; Strayer, David S.

doi:10.1086/340210

Cited by 18 publications

(9 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of intrabodies in other cell-based systems have not been reported to alter growth and development. [64][65][66] Although CCR5 intrabody expression is functional and limits the amount and duration of viral spread at the population level in CD4 + T cells isolated from the human thymus (Figure 3), additional studies are required to determine the variability of CAD-R5-mediated protection provided to individual CD4 + T cells derived from transduced CD34 + progenitors.…”

Section: Ccr5 Intrabody-mediated Protection and Enrichment Of T Cellsmentioning

confidence: 99%

T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery

et al. 2006

View full text Add to dashboard Cite

CCR5 is the chemokine co-receptor for R5-tropic human immunodeficiency virus type 1 (HIV-1) isolates most often associated with primary infection. We have developed an HIV-1 self-inactivating vector, CAD-R5, containing a CCR5 single-chain antibody (intrabody) gene, which when expressed in T-cell lines and primary CD4 + T cells disrupts CCR5 cell surface expression and provides protection from R5-tropic isolate exposure. Furthermore, CAD-R5 intrabody expression in primary CD4 + T cells supports significant growth and enrichment over time during HIV-1-pulsed dendritic cell-T-cell interactions. These results indicate that CCR5 intrabody-expressing CD4 + T cells are refractory against this highly efficient primary route of infection. CD34 + cells transduced with the CAD-R5 vector gave rise to CD4 + and CD8 + thymocytes in non-obese diabetic (NOD)/ severely combined-immunodeficient (SCID)-human thymus/ liver (hu thy/liv) mice, suggesting that CCR5 intrabody expression can be maintained throughout differentiation without obvious cellular effects. CD4 + T cells isolated from NOD/SCID-hu thy/liv mice were resistant to R5-tropic HIV-1 challenge demonstrating the maintenance of protection. Our findings demonstrate delivery of anti-HIV-1 activity through CCR5 intrabodies in primary CD4 + T cells and CD34 + cell-derived T-cell progeny. Thus, gene delivery strategies that provide a selective survival and growth advantage for T effector cells may provide a therapeutic benefit for HIV-1-infected individuals who have failed conventional therapies.

show abstract

Section: Ccr5 Intrabody-mediated Protection and Enrichment Of T Cellsmentioning

confidence: 99%

T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery

et al. 2006

View full text Add to dashboard Cite

show abstract

“…These vectors readily transduce neurons in vitro and in vivo, and have been effective in studying gene transfer as protection from HIV-1 in experimental systems. [37][38][39][40][41][42] We found that rSV40 gene delivery of transgenes SOD1 and GPx1, singly or in combination, significantly mitigated neuronal apoptosis mediated by gp120. The effectiveness and degree of protection of these vectors in delivering these antioxidant enzymes was also verified in vivo.…”

Section: Introductionmentioning

confidence: 75%

Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis

et al. 2006

View full text Add to dashboard Cite

“…Our study indicates that a full-length Vp2 is not essential in a productive SV40 infection; it also suggests that the Vp2-unique coding region may be dispensable as long as the Vp3 reading frame and initiating AUG codon are maintained. -Herman et al, 1999;Goldstein et al, 2002). Chang & Wilson (1986) have suggested the packaging limit for SV40 to be between 284 and 460 extra base pairs.…”

mentioning

confidence: 99%

The simian virus 40 minor structural protein Vp3, but not Vp2, is essential for infectious virion formation

Gharakhanian¹,

Munoz²,

Mayorca³

2003

Journal of General Virology

View full text Add to dashboard Cite

The SV40 capsid is composed of pentameric capsomeres of the major structural protein Vp1. The two minor structural proteins, Vp2 and Vp3, interact with the capsid. Here, the roles of Vp2 and Vp3 were explored during the course of SV40 infection. Start codons of Vp2, Vp3, or both Vp2 and Vp3, were destroyed by site-directed mutagenesis, and mutant genomes were transfected into CV-1 cells. SV40DVp2 produced plaques and infectious virion particles with titres indistinguishable from wild-type. SV40DVp3 and SV40 DVp2/Vp3 were defective in plaque formation and rendered no infectious particles. All three mutants showed normal nuclear localization of T-Ag and Vp1; they also showed packaging of SV40 DNA by nuclease digestion assays. Thus, Vp3 is essential for formation of infectious SV40 particles, whereas Vp2 is not. One critical role of full-length Vp3 appears to be in virus-cell interactions at post-packaging steps of a permissive infection.Simian virus 40 (SV40) belongs to the polyomavirus family of DNA tumour viruses. In simian cells, SV40 initiates a permissive infection leading to virion progeny. SV40 entry into cells involves caveolar endocytosis leading to virus accumulation and uncoating in the endoplasmic reticulum (Anderson et al., 1996;Pelkmans et al., 2001;Norkin et al., 2002). Late in permissive infection, the viral structural proteins Vp1, Vp2 and Vp3 are synthesized in the cytoplasm and are transported to the nucleus for assembly of the icosahedral capsid (Tooze, 1980). The capsomeric unit is composed of pentamers of Vp1. In polyomavirus, each Vp1 pentamer is tightly associated with one Vp2 or Vp3 molecule through hydrophobic interactions (Barouch & Harrison, 1994;Chen et al., 1998). Vp2 and Vp3 bridge Vp1 capsomeres to the SV40 genome which is complexed into nucleosomes with cellular histones (Rayment et al., 1982;Baker et al., 1988; Liddington et al., 1991;Stehle et al., 1996). The entire 234 amino acid sequence of Vp3 is repeated in the C terminus of a myristylated Vp2, leaving 118 unique residues at the Vp2 N terminus. Several functions have been mapped to the C-terminal 40 amino acids common to both Vp2 and Vp3 (Vp2/3). They include a DNA-binding domain and a nuclear localization signal (Gharakhanian et al., 1987(Gharakhanian et al., , 1988Gharakhanian & Kasamatsu, 1990;Clever et al., 1991Clever et al., , 1993Dean et al., 1995). A Vp1-binding domain has been mapped to an internal domain in the Vp2/3 common region (Gordon-Shaag et al., 2002). Yet, not much is known about the significance of the Vp2-specific 118 residues. Recently, Mannova et al. (2002) SV40 DVp2, SV40DVp3 and SV40DVp2/Vp3 genomes were generated by site-directed mutagenesis of the initiation codons of Vp2, Vp3, or both Vp2 and Vp3, respectively, in the parent plasmid pSV40 (Transformer Kit, Clontech). The mammalian expression vector pSV40 contains the wild-type SV40 genome and has been described before (Clever & Kasamatsu, 1993 (Fig. 1b, c); in repeated experiments, onset of CPE for wild-type-and SV40DVp2-transfected cells was identi...

show abstract

Gene Therapy Using a Simian Virus 40–Derived Vector Inhibits the Development of In Vivo Human Immunodeficiency Virus Type 1 Infection of Severe Combined Immunodeficiency Mice Implanted with Human Fetal Thymic and Liver Tissue

Cited by 18 publications

References 21 publications

T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery

T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery

Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis

The simian virus 40 minor structural protein Vp3, but not Vp2, is essential for infectious virion formation

Contact Info

Product

Resources

About