scholarly journals Mutation of the BAFF furin cleavage site impairs B-cell homeostasis and antibody responses

2011 ◽  
Vol 41 (3) ◽  
pp. 787-797 ◽  
Author(s):  
Claudia Bossen ◽  
Aubry Tardivel ◽  
Laure Willen ◽  
Carrie A. Fletcher ◽  
Mai Perroud ◽  
...  
Keyword(s):  
B Cell ◽  
Cleavage Site ◽  
Antibody Responses ◽  
Furin Cleavage ◽  
Cell Homeostasis ◽  
Furin Cleavage Site ◽  
B Cell Homeostasis

scholarly journals O-GlcNAcylation is required for B cell homeostasis and antibody responses

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Jung-Lin Wu ◽  
Ming-Feng Chiang ◽  
Pan-Hung Hsu ◽  
Dong-Yen Tsai ◽  
Kuo-Hsuan Hung ◽  
...  
Keyword(s):  
B Cell ◽  
Antibody Responses ◽  
Cell Homeostasis ◽  
B Cell Homeostasis

scholarly journals Targeting of Ly9 (CD229) Disrupts Marginal Zone and B1 B Cell Homeostasis and Antibody Responses

2015 ◽  
Vol 196 (2) ◽  
pp. 726-737 ◽  
Author(s):  
Marta Cuenca ◽  
Xavier Romero ◽  
Jordi Sintes ◽  
Cox Terhorst ◽  
Pablo Engel
Keyword(s):  
B Cell ◽  
Marginal Zone ◽  
Antibody Responses ◽  
Cell Homeostasis ◽  
B Cell Homeostasis

Disturbed B-cell homeostasis in pediatric cGvHD patients

2015 ◽  
Vol 227 (03) ◽  
Author(s):  
J Zipfel ◽  
M Eyrich ◽  
PG Schlegel ◽  
V Wiegering
Keyword(s):  
B Cell ◽  
Cell Homeostasis ◽  
B Cell Homeostasis

scholarly journals Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation

2021 ◽  
Vol 118 (47) ◽  
pp. e2109905118
Author(s):  
Liping Zhang ◽  
Matthew Mann ◽  
Zulfeqhar A. Syed ◽  
Hayley M. Reynolds ◽  
E. Tian ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Protein S ◽  
Viral Infectivity ◽  
The Novel ◽  
Furin Cleavage ◽  
Global Pandemic ◽  
Furin Cleavage Site ◽  
Respiratory Cells ◽  
Syncytia Formation

The SARS-CoV-2 coronavirus responsible for the global pandemic contains a novel furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation in cells. Here, we show that O-glycosylation near the furin cleavage site is mediated by members of the GALNT enzyme family, resulting in decreased furin cleavage and decreased syncytia formation. Moreover, we show that O-glycosylation is dependent on the novel proline at position 681 (P681). Mutations of P681 seen in the highly transmissible alpha and delta variants abrogate O-glycosylation, increase furin cleavage, and increase syncytia formation. Finally, we show that GALNT family members capable of glycosylating S are expressed in human respiratory cells that are targets for SARS-CoV-2 infection. Our results suggest that host O-glycosylation may influence viral infectivity/tropism by modulating furin cleavage of S and provide mechanistic insight into the role of the P681 mutations found in the highly transmissible alpha and delta variants.

scholarly journals SARS-CoV-2 Origin: An Affair of Codons?

2021 ◽  
Author(s):  
Antonio Ramón Romeu ◽  
Enric Ollé
Keyword(s):  
Human Genome ◽  
Genetic Markers ◽  
Cleavage Site ◽  
Cleavage Sites ◽  
Furin Cleavage ◽  
Large Sample ◽  
The Core ◽  
Furin Cleavage Site

The furin cleavage site, with an arginine doublet (RR), is one of the clues of the SARS-CoV-2 origin. This furin-RR is encoded by the CGG-CGG sequence. Because arginine can be encoded by six codons, in a previous work we found that in SARS-CoV-2, CGG was the minority arginine codon (3%). Also, analyzing the RR doublet from a large sample of furin cleavage sites of several kinds of viruses, we found that none of them were encoded by CGG-CGG. Here, we come back to the core of the matter, but from the perspective that in the human genome, in contrast, CGG is the majoroty arginine codon (21%). Here, we highlighted that the 6 arginine codons provide genetic markers to a traceability on the RR origin in the furin site, as well as, to weigh the probability of the theories about the origin of the virus.

Disturbed B Cell Homeostasis in Newly Diagnosed Giant Cell Arteritis and Polymyalgia Rheumatica

2014 ◽  
Vol 66 (7) ◽  
pp. 1927-1938 ◽  
Author(s):  
Kornelis S. M. van der Geest ◽  
Wayel H. Abdulahad ◽  
Paulina Chalan ◽  
Abraham Rutgers ◽  
Gerda Horst ◽  
...  
Keyword(s):  
B Cell ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Polymyalgia Rheumatica ◽  
Newly Diagnosed ◽  
Cell Homeostasis ◽  
B Cell Homeostasis

scholarly journals Furin-Mediated Cleavage of the Feline Foamy Virus Env Leader Protein

2004 ◽  
Vol 78 (24) ◽  
pp. 13573-13581 ◽  
Author(s):  
Verena Geiselhart ◽  
Patrizia Bastone ◽  
Tore Kempf ◽  
Martina Schnölzer ◽  
Martin Löchelt
Keyword(s):  
Cleavage Site ◽  
Transmembrane Protein ◽  
Foamy Virus ◽  
Proteolytic Processing ◽  
Signal Peptidase ◽  
Amino Acid Residues ◽  
Furin Cleavage ◽  
Furin Cleavage Site ◽  
Leader Protein ◽  
Distinguishing Features

ABSTRACT The molecular biology of spuma or foamy retroviruses is different from that of the other members of the Retroviridae. Among the distinguishing features, the N-terminal domain of the foamy virus Env glycoprotein, the 16-kDa Env leader protein Elp, is a component of released, infectious virions and is required for particle budding. The transmembrane protein Elp specifically interacts with N-terminal Gag sequences during morphogenesis. In this study, we investigate the mechanism of Elp release from the Env precursor protein. By a combination of genetic, biochemical, and biophysical methods, we show that the feline foamy virus (FFV) Elp is released by a cellular furin-like protease, most likely furin itself, generating an Elp protein consisting of 127 amino acid residues. The cleavage site fully conforms to the rules for an optimal furin site. Proteolytic processing at the furin cleavage site is required for full infectivity of FFV. However, utilization of other furin proteases and/or cleavage at a suboptimal signal peptidase cleavage site can partially rescue virus viability. In addition, we show that FFV Elp carries an N-linked oligosaccharide that is not conserved among the known foamy viruses.

Lymph node formation and B cell homeostasis require IKK-α in distinct endothelial cell–derived compartments

2021 ◽  
Vol 118 (48) ◽  
pp. e2100195118
Author(s):  
Kelly A. McCorkell ◽  
Nipun Jayachandran ◽  
Michelle D. Cully ◽  
Jacquelyn Freund-Brown ◽  
Tiffany Weinkopff ◽  
...  
Keyword(s):  
Lymph Node ◽  
B Cell ◽  
Vascular Endothelial Cells ◽  
Hematopoietic Cells ◽  
Lymphatic Vessels ◽  
Cell Homeostasis ◽  
Cell Numbers ◽  
Iκb Kinase ◽  
Physiologic Function ◽  
B Cell Homeostasis

Global inactivation of IκB kinase (IKK)-α results in defective lymph node (LN) formation and B cell maturation, and loss of IKK-α–dependent noncanonical NF-κB signaling in stromal organizer and hematopoietic cells is thought to underlie these distinct defects. We previously demonstrated that this pathway is also activated in vascular endothelial cells (ECs). To determine the physiologic function of EC-intrinsic IKK-α, we crossed IkkαF/F mice with Tie2-cre or Cdh5-cre mice to ablate IKK-α in ECs. Notably, the compound defects of global IKK-α inactivation were recapitulated in IkkαTie2 and IkkαCdh5 mice, as both lacked all LNs and mature follicular and marginal zone B cell numbers were markedly reduced. However, as Tie2-cre and Cdh5-cre are expressed in all ECs, including blood forming hemogenic ECs, IKK-α was also absent in hematopoietic cells (HC). To determine if loss of HC-intrinsic IKK-α affected LN development, we generated IkkαVav mice lacking IKK-α in only the hematopoietic compartment. While mature B cell numbers were significantly reduced in IkkαVav mice, LN formation was intact. As lymphatic vessels also arise during development from blood ECs, we generated IkkαLyve1 mice lacking IKK-α in lymphatic ECs (LECs) to determine if IKK-α in lymphatic vessels impacts LN development. Strikingly, while mature B cell numbers were normal, LNs were completely absent in IkkαLyve1 mice. Thus, our findings reveal that IKK-α in distinct EC-derived compartments is uniquely required to promote B cell homeostasis and LN development, and we establish that LEC-intrinsic IKK-α is absolutely essential for LN formation.

Sign in / Sign up

Export Citation Format

Share Document