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

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 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

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

Human endogenous retrovirus type W envelope protein inhibits oligodendroglial precursor cell differentiation

2013 ◽  
Vol 74 (5) ◽  
pp. 721-732 ◽  
Author(s):  
David Kremer ◽  
Tanja Schichel ◽  
Moritz Förster ◽  
Nevena Tzekova ◽  
Corinne Bernard ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Precursor Cell ◽  
Human Endogenous Retrovirus

scholarly journals Vaccination Directed against the Human Endogenous Retrovirus-K Envelope Protein Inhibits Tumor Growth in a Murine Model System

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72756 ◽  
Author(s):  
Benjamin Kraus ◽  
Katrin Fischer ◽  
Sarah M. Büchner ◽  
Winfried S. Wels ◽  
Roswitha Löwer ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Murine Model ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Model System ◽  
Human Endogenous Retrovirus

The neutralizing antibody GNbAC1 abrogates HERV-W envelope protein-mediated oligodendroglial maturation blockade

2014 ◽  
Vol 21 (9) ◽  
pp. 1200-1203 ◽  
Author(s):  
David Kremer ◽  
Moritz Förster ◽  
Tanja Schichel ◽  
Peter Göttle ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Envelope Protein ◽  
Nitrosative Stress ◽  
Immune Cell ◽  
Neutralizing Antibody ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Stress Reactions ◽  
Induce Stress ◽  
Inflammatory Reactions

Background: The envelope protein (ENV) of the human endogenous retrovirus type W is implicated in inflammatory reactions in multiple sclerosis (MS) but also interferes with oligodendroglial maturation. A neutralizing antibody GNbAC1 has been developed and successfully been tested in clinical trials. Objectives and methods: We stimulated primary oligodendroglial cells with ENV upon preincubation with GNbAC1 and assessed for nitrosative stress and myelin expression. Results: Neutralization of ENV by GNbAC1 reduces its ability to induce stress reactions resulting in a rescue of myelin expression. Conclusions: Beyond immune cell modulation, this monoclonal antibody may therefore help to overcome the oligodendroglial differentiation blockade in MS.

scholarly journals The Envelope Protein of a Human Endogenous Retrovirus-W Family Activates Innate Immunity through CD14/TLR4 and Promotes Th1-Like Responses

2006 ◽  
Vol 176 (12) ◽  
pp. 7636-7644 ◽  
Author(s):  
Alexandre Rolland ◽  
Evelyne Jouvin-Marche ◽  
Christophe Viret ◽  
Mathias Faure ◽  
Hervé Perron ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus
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