Lentiviral gene delivery to plasmolipin-expressing cells using Mus caroli endogenous retrovirus envelope protein

Biochimie ◽  
2017 ◽  
Vol 142 ◽  
pp. 226-233 ◽  
Author(s):  
M.M. Prokofjeva ◽  
G.M. Proshkina ◽  
T.D. Lebedev ◽  
A.A. Shulgin ◽  
P.V. Spirin ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Mus Caroli

CSIG-24. TARGETED INHIBITION OF CDK5-MEDIATED REGULATION OF HUMAN ENDOGENOUS RETROVIRUS K (HML-2) ENVELOPE PROTEIN IN ATYPICAL TERATOID RHABDOID TUMOR

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi38-vi38
Author(s):  
Tara Doucet-O'Hare ◽  
Jared Rosenblum ◽  
Brianna DiSanza ◽  
Catherine DeMarino ◽  
Abigail Atkinson ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Envelope Protein ◽  
Phosphorylation Site ◽  
Endogenous Retrovirus ◽  
Rhabdoid Tumor ◽  
Human Endogenous Retrovirus ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Atypical Teratoid ◽  
Targeted Inhibition

Abstract Atypical teratoid rhabdoid tumor (ATRT) is a pediatric brain tumor with a high mortality rate characterized by mutations in/ deletions of SWI/SNF matrix-associated actin-dependent regulator of chromatin sub-family B member 1 (SMARCB1). We previously showed that loss of SMARCB1 causes up-regulation and release of HML-2 subfamily of human endogenous retrovirus K envelope protein (HML-2 ENV), resulting in maintenance of pluripotency. Here, we investigated intracellular trafficking and release of HML-2 ENV. Further, we demonstrate two potential therapeutic strategies to decrease intracellular HML-2 ENV: 1) inhibition of calcium influx by ouabain, a cardiac glycoside toxic to neural stem cells, and 2) targeted inhibition of cyclin-dependent kinase 5 (CDK5), which is restricted to neurons by p35, its activator protein, by TP5. ATRT cell lines and tumor tissue obtained from patients were confirmed for SMARCB1 loss and increased HML-2 ENV. Cell viability and intracellular HML-2 ENV concentration were measured after treatment with ouabain and TP5 (CDK5 antagonist). We evaluated the calcium-mediated effect of ouabain on HML-2 intracellular concentration by treating the cells with ouabain, the calcium chelators calcimycin and EGTA, and calpeptin, a calpain inhibitor, which activates CDK5, and measuring HML-2 ENV and p35. We evaluated HML-2 ENV for a CDK5 consensus phosphorylation site and performed co-immunoprecipitation to evaluate direct interaction. We evaluated activity of CDK5 in ATRT cell lines by autoradiography. Both Ouabain and TP5 caused a decrease in cell viability in a dose-dependent manner. Further, ouabain treatment decreased HML-2 ENV intracellular concentration. We found that HML-2 ENV contains a consensus phosphorylation site for CDK5. We discovered that HML-2 ENV was bound to CDK5. We established that ATRT cell lines had hyperactive CDK5. Finally, we established that the effect of ouabain on HML-2 ENV was due to indirect inhibition of calcium-mediated activation of calpain and thus CDK5.

scholarly journals The HERV-K Human Endogenous Retrovirus Envelope Protein Antagonizes Tetherin Antiviral Activity

2014 ◽  
Vol 88 (23) ◽  
pp. 13626-13637 ◽  
Author(s):  
C. Lemaitre ◽  
F. Harper ◽  
G. Pierron ◽  
T. Heidmann ◽  
M. Dewannieux
Keyword(s):  
Antiviral Activity ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus

Establishing the Reactivity of Monoclonal Antibodies against Porcine Endogenous Retrovirus Envelope Protein

Intervirology ◽  
2004 ◽  
Vol 47 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Shih-Rong Wang ◽  
Jen-Ting Chang ◽  
Meng-Shiue Lin ◽  
Chen-Yi Chiang ◽  
Hwan-You Chang
Keyword(s):  
Monoclonal Antibodies ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Porcine Endogenous Retrovirus

scholarly journals An N-terminally truncated envelope protein encoded by a human endogenous retrovirus W locus on chromosome Xq22.3

Retrovirology ◽  
2010 ◽  
Vol 7 (1) ◽  
pp. 69 ◽  
Author(s):  
Christina Roebke ◽  
Silke Wahl ◽  
Georg Laufer ◽  
Christine Stadelmann ◽  
Marlies Sauter ◽  
...  
Keyword(s):  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus

scholarly journals Co-option of an endogenous retrovirus envelope for host defense in hominid ancestors

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Daniel Blanco-Melo ◽  
Robert J Gifford ◽  
Paul D Bieniasz
Keyword(s):  
Host Defense ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Monocarboxylate Transporter ◽  
Close Relative ◽  
Cell Surfaces ◽  
Molecular Fossil ◽  
Monocarboxylate Transporter 1 ◽  
The Past ◽  
Functional Envelope

Endogenous retroviral sequences provide a molecular fossil record of ancient infections whose analysis might illuminate mechanisms of viral extinction. A close relative of gammaretroviruses, HERV-T, circulated in primates for ~25 million years (MY) before apparent extinction within the past ~8 MY. Construction of a near-complete catalog of HERV-T fossils in primate genomes allowed us to estimate a ~32 MY old ancestral sequence and reconstruct a functional envelope protein (ancHTenv) that could support infection of a pseudotyped modern gammaretrovirus. Using ancHTenv, we identify monocarboxylate transporter-1 (MCT-1) as a receptor used by HERV-T for attachment and infection. A single HERV-T provirus in hominid genomes includes an env gene (hsaHTenv) that has been uniquely preserved. This apparently exapted HERV-T env could not support virion infection but could block ancHTenv mediated infection, by causing MCT-1 depletion from cell surfaces. Thus, hsaHTenv may have contributed to HERV-T extinction, and could also potentially regulate cellular metabolism.

scholarly journals Development of Zika Virus DNA Vaccine Using Envelope Modified Baculoviral Gene Delivery System

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 85
Author(s):  
Hanul Choi ◽  
Yuyeon Jang ◽  
Hansam Cho ◽  
Ha Youn Shin ◽  
Young Bong Kim
Keyword(s):  
Gene Delivery ◽  
Dna Vaccine ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Challenge Test ◽  
Recombinant Baculovirus ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Cmv Promoter ◽  
Wide Range

Zika virus (ZIKV) is a mosquito-borne flavivirus and the infection of pregnant women can cause a wide range of congenital abnormalities, including microcephaly in the infant. However, there is no vaccine available yet. In this study, we intended to use PrM/E, which is the main target gene of neutralizing antibodies, for the development of a DNA vaccine for ZIKV. To enhance the gene delivery, a recombinant baculovirus whose surface was modified to express human endogenous retrovirus (HERV) envelope was constructed. Baculovirus with HERV envelope (AcHERV) showed distinguished higher gene delivery than wild type. Using the AcHERV as a delivery vector, we constructed major antigen (prM-E)-encoding DNA under the CMV promoter, AcHERV–ZIKA. Transducing of prM/E gene in a mammalian cell was confirmed by Western blot. Immunization in mice with 10e7 of AcHERV–ZIKA elicited high IgG and neutralizing antibodies. In the challenge test, AcHERV–ZIKA immunized A129 mice showed perfect protection. These results suggest that AcHERV–ZIKA could be a potential vaccine candidate for human application.

Rescuing the negative impact of human endogenous retrovirus envelope protein on oligodendroglial differentiation and myelination

Glia ◽  
2018 ◽  
Vol 67 (1) ◽  
pp. 160-170 ◽  
Author(s):  
Peter Göttle ◽  
Moritz Förster ◽  
Joel Gruchot ◽  
David Kremer ◽  
Hans Peter Hartung ◽  
...  
Keyword(s):  
Envelope Protein ◽  
Negative Impact ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus

scholarly journals Identification of the Myelin Protein Plasmolipin as the Cell Entry Receptor for Mus caroli Endogenous Retrovirus

2008 ◽  
Vol 82 (14) ◽  
pp. 6862-6868 ◽  
Author(s):  
A. Dusty Miller ◽  
Ulla Bergholz ◽  
Marion Ziegler ◽  
Carol Stocking
Keyword(s):  
Cell Line ◽  
Hybrid Cell ◽  
Receptor Gene ◽  
Wild Mouse ◽  
Cell Types ◽  
Mouse Cell ◽  
Endogenous Retrovirus ◽  
Receptor Activity ◽  
Endogenous Virus ◽  
Mus Caroli

ABSTRACT The Asian wild mouse species Mus caroli harbors an endogenous retrovirus (McERV) that is closely related to but distinct from the endogenous retrovirus family defined by the Mus dunni endogenous virus and the Mus musculus endogenous retrovirus. McERV could infect some cell types from humans, dogs, and rats, but not all, and did not infect any mouse cell line tested. Because of its interesting host range and proposed ancestral relationship to primate retroviruses and because none of the entry receptors for this family of retroviruses had been identified, we began a search for the McERV receptor. We determined the chromosomal location of the receptor gene in the human genome by phenotypic screening of the G3 human-hamster radiation hybrid cell line panel and confirmed the localization by assaying for receptor activity conferred by bacterial artificial chromosome (BAC) clones spanning the region. We next localized the gene more precisely in one positive BAC by assaying for receptor activity following BAC digestion with several restriction enzymes that cleaved different sets of genes, and we confirmed that the final candidate gene, plasmolipin (PLLP; TM4SF11), is the novel receptor by showing that the expression of the human PLLP cDNA renders hamster and mouse cells susceptible to McERV infection. PLLP functions as a voltage-dependent potassium ion channel and is expressed primarily in kidney and brain, helping to explain the limited range of cell types that McERV can infect. Interestingly, mouse PLLP also functioned well as a receptor for McERV but was simply not expressed in the mouse cell types that we originally tested.

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