Nipah Virus Envelope-Pseudotyped Lentiviruses Efficiently Target ephrinB2-Positive Stem Cell Populations
            <i>In Vitro</i>
            and Bypass the Liver Sink When Administered
            <i>In Vivo</i>

Palomares, Karina; Vigant, Frédéric; Handel, Ben Van; Pernet, Olivier; Chikere, Kelechi; Hong, Patrick; Sherman, Sean P.; Patterson, Michaela; An, Dong Sung; Lowry, William E.; Mikkola, Hanna; Morizono, Kouki; Lee, Benhur

doi:10.1128/jvi.00279-13

Cited by 3 publications

(2 citation statements)

References 2 publications

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“…Although the neutralization problem was solved by the engineering of the Tupaia paramyxovirus (TPMV) glycoproteins, these modified viruses are not also produced at high titers . Some previous studies have demonstrated that LVs can be receptor‐targeted by the Nipah virus (NiV) glycoproteins, resulting in vector production at high titers . Therefore, NiV glycoproteins appear to be a more appropriate option for generating the pseudotyped LVs than MV or TPMV.…”

Section: Introductionmentioning

confidence: 99%

Design and construction of a recombinant lentiviral vector with specific tropism to human epidermal growth factor‐overexpressed cancer cells: Developing a new retargeting system for lentivirus vectors

Ebrahimabadi

Shahbazi

Akbari

et al. 2019

The Journal of Gene Medicine

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Background Targeting of specific tissues and cells by viruses is one of the challenges faced by researchers. Lentiviral vectors (LVs) are one of the most promising gene delivery systems in cancer gene therapy. Therefore, we aimed to design a novel lentiviral delivery system that expresses anti‐ human epidermal growth factor 2 (HER2) designed anykrin repeat protein (DARPin) on the vector envelope to create a pseudotyped lentivirus for targeting HER2‐positive cancer cells. Methods A helper plasmid producing the viral vector envelope containing anti‐HER2 DARPin‐G3 was constructed. LV was produced by transfer vector containing green fluorescent protein (GFP) gene and helper plasmids in human embryonic kidney 293 cells. The human breast cancer cell lines SKBR3 (normal and with inhibited endocytosis) (HER2‐positive) and MDA‐MB‐231 (HER2‐negative) were transduced by the recombinant viral vector. The GFP‐based transduction rate was determined by flow cytometry and fluorescence microscopy. Results The anti‐HER2 DARPin concentration in DARPin‐LVs was significantly higher than the envelope G glycoprotein of the vesicular stomatitis virus‐LVs (non‐anti‐HER2 control) (p < 0.0001). In flow cytometry assays, the percentage of transduction by recombinant LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0074) and MDA‐MB‐231 cells (p = 0.0037). In fluorescence microscopy assays, the percentage of transduction by new LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0026) and MDA‐MB‐231 cells (p = 0.0014). Conclusions We constructed a new recombinant LV with a defect in cell entry directly, containing an anti‐HER2 DARPin on the vector envelope with specific tropism to HER2 receptor on HER2‐positive cancer cells. We assumed that this viral vector transduces cells via an endocytosis‐dependent process.

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Section: Introductionmentioning

confidence: 99%

Design and construction of a recombinant lentiviral vector with specific tropism to human epidermal growth factor‐overexpressed cancer cells: Developing a new retargeting system for lentivirus vectors

Ebrahimabadi

Shahbazi

Akbari

et al. 2019

The Journal of Gene Medicine

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“…The molecular mechanisms underlying the recruitment of foreign glycoproteins to budding viral particles are not understood. However, such pseudotyped viruses can be used as a gene delivery tool to direct viruses to a specific cell type (5)(6)(7)(8)(9)(10).…”

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confidence: 99%

Retrovirus Glycoprotein Functionality Requires Proper Alignment of the Ectodomain and the Membrane-Proximal Cytoplasmic Tail

Janaka

Gregory

Johnson

2013

J Virol

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Nonnative viral glycoproteins, including Friend murine leukemia virus envelope (F-MLV Env) are actively recruited to HIV-1 assembly sites by an unknown mechanism. Because interactions with the lipid microenvironment at budding sites could contribute to recruitment, we examined the contribution of the hydrophobicity of the F-MLV Env membrane-spanning domain (MSD) to its incorporation into HIV-1 particles. A series of F-MLV Env mutants that added or deleted one, two, or three leucines in the MSD were constructed. All six mutants retained the ability to be incorporated into HIV-1 particles, but the ؊1L, ؊2L, ؊3L, ؉1L, and ؉2L mutants were not capable of producing infectious particles. Surprisingly, the ؉3L Env glycoprotein was able to produce infectious particles and was constitutively fusogenic. However, when the cytoplasmic tail domains (CTDs) in the Env constructs were deleted, all six of the MSD mutants were able to produce infectious particles. Further mutational analyses revealed that the first 10 amino acids of the CTD is a critical regulator of infectivity. A similar phenotype was observed in HIV-1 Env upon addition of leucines in the MSD, with ؉1 and ؉2 leucine mutations greatly reducing Env activity, but ؉3 leucine mutations behaving similar to the wild type. Unlike F-MLV Env (؉1L and ؉2L), HIV-1 Env (؉1L and ؉2L) infectivity was not restored by deletion of the CTD. We hypothesize that the CTD forms a coiled-coil that disrupts the protein's functionality if it is not in phase with the trimer interface of the ectodomain. E nveloped viruses assemble by the confluence of structural proteins, genetic material, and surface glycoproteins. Glycoprotein-deficient viruses have the potential to be complemented by diverse, nonnative viral glycoproteins in a process termed pseudotyping (reviewed in references 1 to 4). The molecular mechanisms underlying the recruitment of foreign glycoproteins to budding viral particles are not understood. However, such pseudotyped viruses can be used as a gene delivery tool to direct viruses to a specific cell type (5-10).Retroviral Env glycoproteins are produced as precursors that trimerize in the endoplasmic reticulum (ER). Subsequently, the precursor protein is cleaved by furin or a furin-like protease into its constituent subdomains: the surface subunit (SU) containing the receptor binding domain and the transmembrane subunit (TM) containing the fusion-promoting domain. The mature Env is thus a trimer of heterodimers. SU and TM are held together by an intersubunit disulfide bond in the case of alpha-, gamma-, and deltaretroviruses (11-16) and noncovalently associated in the case of lentiviruses and betaretroviruses (17, 18). Upon receptor binding by SU, several conformational changes take place in Env, promoting coreceptor binding and/or accession of the host cell membrane by the fusion peptide in TM (19). For gammaretroviruses, fusogenicity is controlled by the cytoplasmic tail domain (CTD) of Env and isomerization of the disulfide bond between SU and TM (20-22). The C termini ...

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Common Markers and Small Molecule Inhibitors in Golgi Studies

Bui

Stark

et al. 2022

Methods in Molecular Biology

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Nipah Virus Envelope-Pseudotyped Lentiviruses Efficiently Target ephrinB2-Positive Stem Cell Populations In Vitro and Bypass the Liver Sink When Administered In Vivo

Cited by 3 publications

References 2 publications

Design and construction of a recombinant lentiviral vector with specific tropism to human epidermal growth factor‐overexpressed cancer cells: Developing a new retargeting system for lentivirus vectors

Design and construction of a recombinant lentiviral vector with specific tropism to human epidermal growth factor‐overexpressed cancer cells: Developing a new retargeting system for lentivirus vectors

Retrovirus Glycoprotein Functionality Requires Proper Alignment of the Ectodomain and the Membrane-Proximal Cytoplasmic Tail

Common Markers and Small Molecule Inhibitors in Golgi Studies

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