A Retroviral Vector Capable of Targeted Gene Transfer into Cells Expressing HIV Envelope Glycoprotein

2000 ◽  
Vol 271 (3) ◽  
pp. 672-676 ◽  
Author(s):  
Satoru Suzuki ◽  
Takashi Shimada
Keyword(s):  
Gene Transfer ◽  
Envelope Glycoprotein ◽  
Retroviral Vector ◽  
Hiv Envelope

scholarly journals Retrograde Transgene Expression via Neuron-Specific Lentiviral Vector Depends on Both Species and Input Projections

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1387
Author(s):  
Yukiko Otsuka ◽  
Hitomi Tsuge ◽  
Shiori Uezono ◽  
Soshi Tanabe ◽  
Maki Fujiwara ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Immune Responses ◽  
Envelope Glycoprotein ◽  
Transgene Expression ◽  
Histological Analysis ◽  
Lentiviral Vector ◽  
Cortical Input ◽  
Input System ◽  
Vesicular Stomatitis ◽  
Retrograde Gene Transfer

For achieving retrograde gene transfer, we have so far developed two types of lentiviral vectors pseudotyped with fusion envelope glycoprotein, termed HiRet vector and NeuRet vector, consisting of distinct combinations of rabies virus and vesicular stomatitis virus glycoproteins. In the present study, we compared the patterns of retrograde transgene expression for the HiRet vs. NeuRet vectors by testing the cortical input system. These vectors were injected into the motor cortex in rats, marmosets, and macaques, and the distributions of retrograde labels were investigated in the cortex and thalamus. Our histological analysis revealed that the NeuRet vector generally exhibits a higher efficiency of retrograde gene transfer than the HiRet vector, though its capacity of retrograde transgene expression in the macaque brain is unexpectedly low, especially in terms of the intracortical connections, as compared to the rat and marmoset brains. It was also demonstrated that the NeuRet but not the HiRet vector displays sufficiently high neuron specificity and causes no marked inflammatory/immune responses at the vector injection sites in the primate (marmoset and macaque) brains. The present results indicate that the retrograde transgene efficiency of the NeuRet vector varies depending not only on the species but also on the input projections.

Feasibility of Retroviral Vector-Mediated in utero Gene Transfer to the Fetal Rabbit

2005 ◽  
Vol 20 (6) ◽  
pp. 485-493 ◽  
Author(s):  
Rafael Moreno ◽  
Marta Rosal ◽  
Lluis Cabero ◽  
Eduard Gratacós ◽  
Josep M. Aran
Keyword(s):  
Gene Transfer ◽  
Retroviral Vector ◽  
In Utero

scholarly journals HIV envelope tail truncation confers resistance to SERINC5 restriction

2021 ◽  
Vol 118 (21) ◽  
pp. e2101450118
Author(s):  
Tafhima Haider ◽  
Xenia Snetkov ◽  
Clare Jolly
Keyword(s):  
T Cells ◽  
Envelope Glycoprotein ◽  
Cytoplasmic Tail ◽  
Restriction Factor ◽  
Viral Fusion ◽  
Restriction Factors ◽  
Complete Resistance ◽  
Hiv Envelope ◽  
Hiv 1

SERINC5 is a potent lentiviral restriction factor that gets incorporated into nascent virions and inhibits viral fusion and infectivity. The envelope glycoprotein (Env) is a key determinant for SERINC restriction, but many aspects of this relationship remain incompletely understood, and the mechanism of SERINC5 restriction remains unresolved. Here, we have used mutants of HIV-1 and HIV-2 to show that truncation of the Env cytoplasmic tail (ΔCT) confers complete resistance of both viruses to SERINC5 and SERINC3 restriction. Critically, fusion of HIV-1 ΔCT virus was not inhibited by SERINC5 incorporation into virions, providing a mechanism to explain how EnvCT truncation allows escape from restriction. Neutralization and inhibitor assays showed ΔCT viruses have an altered Env conformation and fusion kinetics, suggesting that EnvCT truncation dysregulates the processivity of entry, in turn allowing Env to escape targeting by SERINC5. Furthermore, HIV-1 and HIV-2 ΔCT viruses were also resistant to IFITMs, another entry-targeting family of restriction factors. Notably, while the EnvCT is essential for Env incorporation into HIV-1 virions and spreading infection in T cells, HIV-2 does not require the EnvCT. Here, we reveal a mechanism by which human lentiviruses can evade two potent Env-targeting restriction factors but show key differences in the capacity of HIV-1 and HIV-2 to exploit this. Taken together, this study provides insights into the interplay between HIV and entry-targeting restriction factors, revealing viral plasticity toward mechanisms of escape and a key role for the long lentiviral EnvCT in regulating these processes.

Immunization strategies to augment oral vaccination with DNA and viral vectors expressing HIV envelope glycoprotein

Vaccine ◽  
2002 ◽  
Vol 20 (9-10) ◽  
pp. 1295-1307 ◽  
Author(s):  
Andrzej Wierzbicki ◽  
Irena Kiszka ◽  
Hiroshi Kaneko ◽  
Dariusz Kmieciak ◽  
Thomas J Wasik ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Viral Vectors ◽  
Oral Vaccination ◽  
Immunization Strategies ◽  
Hiv Envelope

Genes transferred by retroviral vectors into normal and mutant myoblasts in primary cultures are expressed in myotubes

1990 ◽  
Vol 10 (6) ◽  
pp. 3268-3271
Author(s):  
B F Smith ◽  
R K Hoffman ◽  
U Giger ◽  
J H Wolfe
Keyword(s):  
Gene Transfer ◽  
Primary Cultures ◽  
Muscle Cells ◽  
Retroviral Vectors ◽  
Retroviral Vector ◽  
Enzyme Deficiency ◽  
Transfer Genes

Retroviral vectors were used to transfer genes efficiently into rat and dog myoblasts in primary cultures under conditions which permitted the transduced myoblasts to differentiate into myotubes expressing the transferred genes. The transduced myotubes expressed normal markers of differentiation and were morphologically indistinguishable from uninfected myotubes. Retroviral vector-mediated gene transfer was also used to correct a genetic enzyme deficiency in mutant canine muscle cells.

scholarly journals Enhanced Green Fluorescent Protein as Selectable Marker of Retroviral-Mediated Gene Transfer in Immature Hematopoietic Bone Marrow Cells

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3304-3315 ◽  
Author(s):  
Marti F.A. Bierhuizen ◽  
Yvonne Westerman ◽  
Trudi P. Visser ◽  
Wati Dimjati ◽  
Albertus W. Wognum ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Green Fluorescent Protein ◽  
Gene Transfer ◽  
Fluorescent Protein ◽  
Bone Marrow Cells ◽  
Retroviral Vector ◽  
Egfp Expression ◽  
Green Fluorescent ◽  
Marrow Cells

Abstract The further improvement of gene transfer into hematopoietic stem cells and their direct progeny will be greatly facilitated by markers that allow rapid detection and efficient selection of successfully transduced cells. For this purpose, a retroviral vector was designed and tested encoding a recombinant version of the Aequorea victoria green fluorescent protein that is enhanced for high-level expression in mammalian cells (EGFP). Murine cell lines (NIH 3T3, Rat2) and bone marrow cells transduced with this retroviral vector demonstrated a stable green fluorescence signal readily detectable by flow cytometry. Functional analysis of the retrovirally transduced bone marrow cells showed EGFP expression in in vitro clonogenic progenitors (GM-CFU), day 13 colony-forming unit-spleen (CFU-S), and in peripheral blood cells and marrow repopulating cells of transplanted mice. In conjunction with fluorescence-activated cell sorting (FACS) techniques EGFP expression could be used as a marker to select for greater than 95% pure populations of transduced cells and to phenotypically define the transduced cells using antibodies directed against specific cell-surface antigens. Detrimental effects of EGFP expression were not observed: fluorescence intensity appeared to be stable and hematopoietic cell growth was not impaired. The data show the feasibility of using EGFP as a convenient and rapid reporter to monitor retroviral-mediated gene transfer and expression in hematopoietic cells, to select for the genetically modified cells, and to track these cells and their progeny both in vitro and in vivo.

scholarly journals Antigen presentation in retroviral vector-mediated gene transfer in vivo

1997 ◽  
Vol 94 (5) ◽  
pp. 1943-1948 ◽  
Author(s):  
E. S. Song ◽  
V. Lee ◽  
C. D. Surh ◽  
A. Lynn ◽  
D. Brumm ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Antigen Presentation ◽  
Retroviral Vector

scholarly journals Expression of a foreign gene in cats reconstituted with retroviral vector infected autologous bone marrow

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 237-245 ◽  
Author(s):  
CD Jr Lothrop ◽  
ZS al-Lebban ◽  
GP Niemeyer ◽  
JB Jones ◽  
MG Peterson ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Bone Marrow ◽  
Gene Transfer ◽  
Autologous Bone Marrow ◽  
Retroviral Vectors ◽  
Retroviral Vector ◽  
Foreign Gene ◽  
Large Animal ◽  
Low Level ◽  
Autologous Bone

Abstract A Moloney murine leukemia virus based retroviral vector was used to transfer the bacterial neomycin resistance gene (neoR) into feline hematopoietic cells. We reconstituted four cats that had been lethally irradiated with autologous bone marrow that had been infected with the N2 or SAX retroviral vector. Bone marrow cells from all four cats expressed the neoR gene 30 days posttransplant and three of four cats still had the neoR gene and a low level of drug resistant colony- forming unit granulocyte-macrophage after more than 200 days. Two of the four cats unexpectedly developed diabetes mellitus 90 days posttransplantation. The expression of a foreign gene in cats, albeit at a low level, demonstrates that retroviral vectors can be used for gene transfer in noninbred large animal species and may be useful for gene therapy of humans. The development of diabetes mellitus in two of the subjects emphasizes the value of animal models for the study of possible deleterious effects of retroviral vector-mediated gene transfer.

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