Impairment of a membrane-targeting protein translated from a downstream gene of a “self-cleaving” T2A peptide conjunction

Hadpech, Sudarat; Jinathep, Wannarat; Saoin, Somphot; Thongkum, Weeraya; Chupradit, Koollawat; Yasamut, Umpa; Moonmuang, Sutpirat; Tayapiwatana, Chatchai

doi:10.1016/j.pep.2018.05.002

Cited by 12 publications

(14 citation statements)

References 29 publications

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“…There is some evidence obtained from neuropharmacological experiments indicating that the VTA-BLA-NAc neural circuit is involved in modulating rewarding effects and motivated behaviors (Di Ciano & Everitt, 2004;Lintas et al, 2011), but direct anatomical evidence still lacks. We determined the putative neuronal circuit using the WGA-Cre transsynaptic tracing technology (Libbrecht et al, 2017;Hadpech et al, 2018), and the results showed that the mCherry labelled BLA neurons received inputs from VTA and sent projections to NAc (Fig 2P-2S), providing neuroanatomical evidence for the VTA-BLA-NAc circuit.…”

Section: Discussionmentioning

confidence: 99%

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The VTA-BLA-NAc circuit for sex reward inhibited by VTA GABAergic neurons under stress in male mice

Yan

Sun

You

et al. 2021

Preprint

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Anhedonia, inability to experience pleasure from rewarding or enjoyable activities, is the prominent symptom of depression that involves dysfunction of the reward processing system. Both genetic predisposition and life events are thought to increase the risk for depression, in particular life stress. The cellular mechanism underlying stress modulating the reward processing neural circuits and subsequently disrupting reward-related behaviors remains elusive. We identify the VTA-BLA-NAc pathway as being activated by sex reward. Blockade of this circuit induces depressive-like behaviors, while reactivation of VTA neurons associated with sexual rewarding experience acutely ameliorates the impairment of reward-seeking behaviors induced by chronic restraint stress. Our histological and electrophysiological results show that the VTA neuron subpopulation responding to restraint stress inhibits the responsiveness of the VTA dopaminergic neurons to sexual reward. Together, these results reveal the cellular mechanism by which stress influences the brain reward processing system and provide a potential target for depression treatment.

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Section: Discussionmentioning

confidence: 99%

“…whose "self-cleaving" would generate two proteins, WGA-Cre and ZsGreen (Hadpech et al, 2018). ZsGreen would label the virus infected VTA neurons ( Fig 2Q) and WGA-Cre would be released into synaptic cleft and taken up by the adjacent neuron (Libbrecht et al, 2017).…”

Section: Vta-bla-nac Pathway Is Activated By Positive Experiencementioning

confidence: 99%

The VTA-BLA-NAc circuit for sex reward inhibited by VTA GABAergic neurons under stress in male mice

Yan

Sun

You

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…However, utilizing several promoters might significantly decrease transcriptional activity and reduce the vector’s packaging capacity. In turn, IRESs provide effective co-expression of a few genes, but their large molecular weight (up to 1 kb) presents a limiting factor [ 49 ]. Moreover, the level of transgene expression depends on the location and spatial organization of the transgene.…”

Section: Introductionmentioning

confidence: 99%

Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors

Gatina

Garanina

Zhuravleva

et al. 2021

IJMS

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Coronary artery disease remains one of the primary healthcare problems due to the high cost of treatment, increased number of patients, poor clinical outcomes, and lack of effective therapy. Though pharmacological and surgical treatments positively affect symptoms and arrest the disease progression, they generally exhibit a limited effect on the disease outcome. The development of alternative therapeutic approaches towards ischemic disease treatment, especially of decompensated forms, is therefore relevant. Therapeutic angiogenesis, stimulated by various cytokines, chemokines, and growth factors, provides the possibility of restoring functional blood flow in ischemic tissues, thereby ensuring the regeneration of the damaged area. In the current study, based on the clinically approved plasmid vector pVax1, multigenic constructs were developed encoding vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF2), and the DsRed fluorescent protein, integrated via picornaviruses’ furin-2A peptide sequences. In vitro experiments demonstrated that genetically modified cells with engineered plasmid constructs expressed the target proteins. Overexpression of VEGF and FGF2 resulted in increased levels of the recombinant proteins. Concomitantly, these did not lead to a significant shift in the general secretory profile of modified HEK293T cells. Simultaneously, the secretome of genetically modified cells showed significant stimulating effects on the formation of capillary-like structures by HUVEC (endothelial cells) in vitro. Our results revealed that when the multicistronic multigene vectors encoding 2A peptide sequences are created, transient transgene co-expression is ensured. The results obtained indicated the mutual synergistic effects of the growth factors VEGF and FGF2 on the proliferation of endothelial cells in vitro. Thus, recombinant multicistronic multigenic constructs might serve as a promising approach for establishing safe and effective systems to treat ischemic diseases.

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“…Stable expression of foreign antigens by the evolved VLV was achieved through the insertion of an RNA sequence encoding the picornavirus T2A ribosome skipping site upstream of VSV-G [ 8 , 9 , 10 ]. However, the T2A site adds extra amino acids to the C-terminal domain of the protein [ 9 ], which may negatively impact protein expression, stability, or secretion, and reduce antibody responses to those antigens [ 8 , 11 ]. Our previous studies with HBV showed that expression of MHBs alone or in combination with other HBV antigens resulted in MHBs-specific T cell activation [ 8 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B

Chiale

Yarovinsky

Mason³

et al. 2020

Vaccines

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Virus-like vesicles (VLV) are hybrid vectors based on an evolved Semliki Forest virus (SFV) RNA replicon and the envelope glycoprotein (G) from vesicular stomatitis virus (VSV). Previously, we showed that VLV can be used to express protein antigens and generate protective antigen-specific CD8+ T cells. This report describes VLV vectors designed for enhanced protein expression and immunogenicity. Expressing hepatitis B virus (HBV) middle S antigen (MHBs) from VLV using a dual subgenomic promoter significantly increased MHBs-specific CD8+ T cell and antibody production in mice. Furthermore, envelope glycoprotein switch from VSV Indiana to the glycoprotein of Chandipura virus enabled prime-boost immunization and further increased responses to MHBs. Therapeutic efficacy was evaluated in a mouse model of chronic HBV infection initiated by HBV delivery with adeno-associated virus. Mice with lower or intermediate HBV antigen levels demonstrated a significant and sustained reduction of HBV replication following VLV prime-boost immunization. However, mice with higher HBV antigen levels showed no changes in HBV replication, emphasizing the importance of HBV antigenemia for implementing immunotherapies. This report highlights the potential of VLV dual promoter vectors to induce effective antigen-specific immune responses and informs the further development and evaluation of hybrid viral vaccine platforms for preventative and therapeutic purposes.

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Impairment of a membrane-targeting protein translated from a downstream gene of a “self-cleaving” T2A peptide conjunction

Cited by 12 publications

References 29 publications

The VTA-BLA-NAc circuit for sex reward inhibited by VTA GABAergic neurons under stress in male mice

The VTA-BLA-NAc circuit for sex reward inhibited by VTA GABAergic neurons under stress in male mice

Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors

Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B

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