scholarly journals Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of coxsackievirus and adenovirus receptor

2021 ◽  
Author(s):  
Hiroki Takeuchi ◽  
Shunsuke Yamaga ◽  
Naoko Sasaki ◽  
Masae Kuboniwa ◽  
Michiya Matsusaki ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Gingival Epithelium ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Adenovirus Receptor

scholarly journals Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of coxsackievirus and adenovirus receptor

2021 ◽  
Author(s):  
Hiroki Takeuchi ◽  
Shunsuke Yamaga ◽  
Naoko Sasaki ◽  
Masae Kuboniwa ◽  
Michiya Matsusaki ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Three Dimensional ◽  
Protein S ◽  
Cysteine Proteases ◽  
Epithelial Barrier ◽  
Epithelial Tissue ◽  
Central Feature ◽  
Tissue Model ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Adenovirus Receptor

Abstract Porphyromonas gingivalis is a major pathogen in severe and chronic manifestations of periodontal disease, which is one of the most common infections of humans. A central feature of P. gingivalis pathogenicity is dysregulation of innate immunity at the gingival epithelial interface. We previously showed that junctional adhesion molecule 1 (JAM1) was specifically degraded by P. gingivalis, leading to epithelial barrier breakdown in gingival tissues. Whereas, the involvement of the other JAM family protein(s) in the epithelial barrier dysregulation by P. gingivalis remains unknown. Here we show that Arg-specific or Lys-specific cysteine proteases named gingipains produced by P. gingivalis specifically degrade coxsackievirus and adenovirus receptor (CXADR), a tight junction associated protein, at R145 and K235 in gingival epithelial cells. A P. gingivalis strain lacking gingipains was impaired in degradation of CXADR. Knockdown of CXADR in a three-dimensional multilayered tissue model increased permeability to 40 kDa dextran, lipopolysaccharide, and proteoglycan. Inversely, overexpression of CXADR in a gingival epithelial tissue model prevented penetration by these agents following P. gingivalis infection. Our findings strongly suggest that P. gingivalis gingipains disrupt barrier function of stratified squamous epithelium via degradation of CXADR as well as JAM1, efficiently allowing bacterial virulence factors to penetrate into subepithelial tissues.

scholarly journals The Coxsackievirus and Adenovirus Receptor: Glycosylation and the Extracellular D2 Domain Are Not Required for Coxsackievirus B3 Infection

2016 ◽  
Vol 90 (12) ◽  
pp. 5601-5610 ◽  
Author(s):  
Sandra Pinkert ◽  
Carsten Röger ◽  
Jens Kurreck ◽  
Jeffrey M. Bergelson ◽  
Henry Fechner
Keyword(s):  
Virus Infection ◽  
Immunoglobulin Superfamily ◽  
Minor Importance ◽  
Receptor Function ◽  
Virus Binding ◽  
D2 Domain ◽  
Cvb3 Infection ◽  
Coxsackie B Viruses ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Adenovirus Receptor

ABSTRACTThe coxsackievirus and adenovirus receptor (CAR) is a member of the immunoglobulin superfamily (IgSF) and functions as a receptor for coxsackie B viruses (CVBs). The extracellular portion of CAR comprises two glycosylated immunoglobulin-like domains, D1 and D2. CAR-D1 binds to the virus and is essential for virus infection; however, it is not known whether D2 is also important for infection, and the role of glycosylation has not been explored. To understand the function of these structural components in CAR-mediated CVB3 infection, we generated a panel of human (h) CAR deletion and substitution mutants and analyzed their functionality as CVB receptors, examining both virus binding and replication. Lack of glycosylation of the CAR-D1 or -D2 domains did not adversely affect CVB3 binding or infection, indicating that the glycosylation of CAR is not required for its receptor functions. Deletion of the D2 domain reduced CVB3 binding, with a proportionate reduction in the efficiency of virus infection. Replacement of D2 with the homologous D2 domain from chicken CAR, or with the heterologous type C2 immunoglobulin-like domain from IgSF11, another IgSF member, fully restored receptor function; however, replacement of CAR-D2 with domains from CD155 or CD80 restored function only in part. These data indicate that glycosylation of the extracellular domain of hCAR plays no role in CVB3 receptor function and that CAR-D2 is not specifically required. The D2 domain may function largely as a spacer permitting virus access to D1; however, the data may also suggest that D2 affects virus binding by influencing the conformation of D1.IMPORTANCEAn important step in virus infection is the initial interaction of the virus with its cellular receptor. Although the role in infection of the extracellular CAR-D1, cytoplasmic, and transmembrane domains have been analyzed extensively, nothing is known about the function of CAR-D2 and the extracellular glycosylation of CAR. Our data indicate that glycosylation of the extracellular CAR domain has only minor importance for the function of CAR as CVB3 receptor and that the D2 domain is not essential per se but contributes to receptor function by promoting the exposure of the D1 domain on the cell surface. These results contribute to our understanding of the coxsackievirus-receptor interactions.

scholarly journals Chimpanzee adenovirus CV-68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor

2002 ◽  
Vol 83 (1) ◽  
pp. 151-155 ◽  
Author(s):  
Christopher J. Cohen ◽  
Zhi Quan Xiang ◽  
Guang-Ping Gao ◽  
Hildegund C. J. Ertl ◽  
James M. Wilson ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Cho Cells ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Soluble Form ◽  
Delivery Vector ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5 ◽  
Dependent Mechanism

A replication-defective form of chimpanzee adenovirus type 68 (C68) has been developed to circumvent problems posed by widespread preexisting immunity to common human adenovirus vectors. To investigate the determinants of C68 tropism, its interaction with the coxsackievirus and adenovirus receptor (CAR) was studied. Although CHO cells were resistant to transduction by C68 as well as by adenovirus type 5 (Ad5), CHO cells expressing either human or murine CAR were transduced readily. C68 transduction, like Ad5 transduction, was blocked when cells were exposed to anti-CAR antibody or when virus was exposed to a soluble form of the CAR extracellular domain. These results indicate that gene delivery by C68 occurs by a CAR-dependent mechanism.

scholarly journals Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart

2008 ◽  
Vol 118 (8) ◽  
pp. 2758-2770 ◽  
Author(s):  
Byung-Kwan Lim ◽  
Dingding Xiong ◽  
Andrea Dorner ◽  
Tae-Jin Youn ◽  
Aaron Yung ◽  
...  
Keyword(s):  
Atrioventricular Node ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Adenovirus Receptor
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