Faculty Opinions recommendation of Molluscum contagiosum virus interleukin-18 (IL-18) binding protein is secreted as a full-length form that binds cell surface glycosaminoglycans through the C-terminal tail and a furin-cleaved form with only the IL-18 binding domain.

ABSTRACT Some poxviruses and their mammalian hosts encode homologous proteins that bind interleukin-18 (IL-18) with high affinity and inhibit IL-18-mediated immune responses. MC54L, the IL-18 binding protein of the human poxvirus that causes molluscum contagiosum, is unique in having a C-terminal tail of nearly 100 amino acids that is dispensable for IL-18 binding. When recombinant MC54L was expressed and purified via a C-terminal six-histidine tag, a shorter fragment was detected in addition to the full-length protein. This C-terminal fragment resulted from the cleavage of MC54L by cellular furin, as it was greatly diminished when furin was specifically inhibited or when a furin-deficient cell line was used for expression. Furthermore, the N- and C-terminal fragments of MC54L were generated by cleavage of the recombinant protein with furin in vitro. The furin cleavage site was mapped within a 32-amino-acid segment that is C terminal to the IL-18 binding domain. Full-length MC54L, but not the N-terminal IL-18 binding fragment, bound to cells and to purified heparin and other glycosaminoglycans that are commonly found on the cell surface and in the extracellular matrix. MC54L bound to heparin with a nanomolar Kd and could simultaneously bind to IL-18. Their different glycosaminoglycan and cell binding properties may allow the long and short forms of MC54L to inactivate IL-18 near the site of infection and at more distal locations, respectively.

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Multifunctional Role of Choline Binding Protein G in Pneumococcal Pathogenesis

Infection and Immunity ◽

10.1128/iai.74.2.821-829.2006 ◽

2006 ◽

Vol 74 (2) ◽

pp. 821-829 ◽

Cited By ~ 37

Author(s):

B. Mann ◽

C. Orihuela ◽

J. Antikainen ◽

G. Gao ◽

J. Sublett ◽

...

Keyword(s):

Serine Proteases ◽

Natural Variation ◽

Binding Protein ◽

Surface Protein ◽

Binding Domain ◽

Full Length ◽

Truncated Protein ◽

Attached Form

ABSTRACT Members of the choline binding protein (Cbp) family are noncovalently bound to phosphorylcholine residues on the surface of Streptococcus pneumoniae. It has been suggested that CbpG plays a role in adherence and increase virulence both at the mucosal surface and in the bloodstream, but the function of this protein has been unclear. A new sequence analysis indicated that CbpG is a possible member of the S1 family of multifunctional surface-associated serine proteases. Clinical isolates contained two alleles of cbpG, and one-third of the strains expressed a truncated protein lacking the C-terminal, cell wall-anchoring choline binding domain. CbpG on the surface of pneumococci (full length) or released into the supernatant (truncated) showed proteolytic activity for fibronectin and casein, as did CbpG expressed on lactobacilli or as a purified full-length or truncated recombinant protein. Recombinant CbpG (rCbpG)-coated beads adhered to eukaryotic cells, and TIGR4 mutants lacking CbpG or having a truncated CbpG protein showed decreased adherence in vitro and attenuation of disease in mouse challenge models of colonization, pneumonia, and bacteremia. Immunization with rCbpG was protective in an animal model of colonization and sepsis. We propose that CbpG is a multifunctional surface protein that in the cell-attached or secreted form cleaves host extracellular matrix and in the cell-attached form participates in bacterial adherence. This is the first example of distinct functions in virulence that are dependent on natural variation in expression of a choline binding domain.

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Evaluating the Humoral Immunity and Interleukin 18 Receptor 1 in some Patients with Molluscum Contagiosum Infection

Baghdad Science Journal ◽

10.21123/bsj.13.1.66-73 ◽

2016 ◽

Vol 13 (1) ◽

pp. 66-73

Author(s):

Baghdad Science Journal

Keyword(s):

Molluscum Contagiosum ◽

The Body ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Interleukin 18 ◽

Molluscum Contagiosum Virus ◽

Significant Difference ◽

The Mean ◽

Diffusion Assay ◽

Igg Level

The molluscum contagiosum virus (MCV) is a dermatotropic poxvirus. The causative agent of molluscum contagiosum (MC) is nonlethal, common and worldwide. Additionally, little inflammation is associated with MC papules. The present study aims to evaluate the immune status of MC patients by measuring the level of immunoglobulins IgG and IgM by using the radial immune diffusion assay (RIA) and the level of interleukin 18 receptor 1 (IL-18R1) by the Enzyme-linked immunosorbent assay (ELISA).The study is conducted during November 2013 to April, 2014 in outpatient clinic of Baquba Teaching Hospital. There are 75 patients, diagnosed with clinical lesions of MCV on different areas of the body, whose age is ranged between 2-50 years including 40(53.3%) males and 35(46.7%) females. The study includes 15 healthy persons age between 2-50 years. The level of IL 18R1 were significantly elevated in patients (677.15±874.22) compared with control (178.46±31.79 ng/ml). There is also a significant elevation in the mean level of serum IgM, where it is 1946.6±825.6 mg/dl while in control group is 140.1±68.7mg/dl. By contrast in patients with lower levels of IgG than the control, the mean serum IgG level in patient is 221.9±96.7 mg/dl while in the control is 1229.9±299.7 mg/dl. Finally, there is no significant difference between MC patients from rural area and urban area.

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Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18-binding proteins

Microbiology ◽

10.1099/0022-1317-81-5-1223 ◽

2000 ◽

Vol 81 (5) ◽

pp. 1223-1230 ◽

Cited By ~ 133

Author(s):

Vincent P. Smith ◽

Neil A. Bryant ◽

Antonio Alcamí

Keyword(s):

Binding Proteins ◽

Viral Infections ◽

Opportunistic Infections ◽

Sequence Similarity ◽

Molluscum Contagiosum ◽

Virus Protein ◽

Interleukin 18 ◽

Molluscum Contagiosum Virus ◽

T Helper 1 ◽

Ifn Γ

Interleukin-18 (IL-18) is a proinflammatory cytokine that plays a key role in the activation of natural killer and T helper 1 cell responses principally by inducing interferon-γ (IFN-γ). Human and mouse secreted IL-18-binding proteins (IL-18BPs) have recently been described which block IL-18 activity but have no sequence similarity to membrane IL-18 receptors. Several poxvirus genes encode proteins with sequence similarity to IL-18BPs. Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response. The ectromelia virus protein was found to block NF-κB activation and induction of IFN-γ in response to IL-18. The highly attenuated vaccinia virus modified virus Ankara encodes IL-18-binding activity, and thus deletion of the vIL-18BP may improve further the safety and immunogenicity of this promising human vaccine candidate. We confirm that molluscum contagiosum virus, a molluscipoxvirus that produces small skin tumours in immunocompetent individuals and opportunistic infections in immunodeficient AIDS patients, also encodes a related, larger vIL-18BP (gene MC54L). This protein may contribute to the lack of inflammatory response characteristic of molluscum contagiosum virus lesions. The expression of vIL-18BPs by distinct poxvirus genera that cause local or general viral dissemination, or persistent or acute infections in the host, emphasizes the importance of IL-18 in response to viral infections.

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Cryo-EM structure of the full-length WzmWzt ABC transporter required for lipid-linked O antigen transport

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2016144118 ◽

2020 ◽

Vol 118 (1) ◽

pp. e2016144118

Author(s):

Christopher A. Caffalette ◽

Jochen Zimmer

Keyword(s):

Cell Surface ◽

Abc Transporter ◽

Bound State ◽

Binding Domain ◽

Full Length ◽

Carbohydrate Binding ◽

Aquifex Aeolicus ◽

O Antigen ◽

Lipid Environment ◽

O Antigens

O antigens are important cell surface polysaccharides in gram-negative bacteria where they extend core lipopolysaccharides in the extracellular leaflet of the outer membrane. O antigen structures are serotype specific and form extended cell surface barriers endowing many pathogens with survival benefits. In the ABC transporter-dependent biosynthesis pathway, O antigens are assembled on the cytosolic side of the inner membrane on a lipid anchor and reoriented to the periplasmic leaflet by the channel-forming WzmWzt ABC transporter for ligation to the core lipopolysaccharides. In many cases, this process depends on the chemical modification of the O antigen’s nonreducing terminus, sensed by WzmWzt via a carbohydrate-binding domain (CBD) that extends its nucleotide-binding domain (NBD). Here, we provide the cryo-electron microscopy structure of the full-length WzmWzt transporter fromAquifex aeolicusbound to adenosine triphosphate (ATP) and in a lipid environment, revealing a highly asymmetric transporter organization. The CBDs dimerize and associate with only one NBD. Conserved loops at the CBD dimer interface straddle a conserved peripheral NBD helix. The CBD dimer is oriented perpendicularly to the NBDs and its putative ligand-binding sites face the transporter to likely modulate ATPase activity upon O antigen binding. Further, our structure reveals a closed WzmWzt conformation in which an aromatic belt near the periplasmic channel exit seals the transporter in a resting, ATP-bound state. The sealed transmembrane channel is asymmetric, with one open and one closed cytosolic and periplasmic portal. The structure provides important insights into O antigen recruitment to and translocation by WzmWzt and related ABC transporters.

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Protein synthesis and cell surface proteins in molluscum contagiosum virus infected cells

Archives of Virology ◽

10.1007/bf01250716 ◽

1973 ◽

Vol 42 (4) ◽

pp. 355-360 ◽

Cited By ~ 1

Author(s):

A. Bernardini ◽

Gloria Barrio ◽

M. Placa

Keyword(s):

Protein Synthesis ◽

Cell Surface ◽

Molluscum Contagiosum ◽

Surface Proteins ◽

Molluscum Contagiosum Virus ◽

Cell Surface Proteins ◽

Infected Cells

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Interleukin-18 and glycosaminoglycan binding by a protein encoded by Variola virus

Journal of General Virology ◽

10.1099/vir.0.79902-0 ◽

2004 ◽

Vol 85 (5) ◽

pp. 1291-1299 ◽

Cited By ~ 30

Author(s):

David J. Esteban ◽

Anthony A. Nuara ◽

R. Mark L. Buller

Keyword(s):

Biological Activity ◽

Host Range ◽

Binding Sites ◽

Binding Activity ◽

Molluscum Contagiosum ◽

Variola Virus ◽

Interleukin 18 ◽

Molluscum Contagiosum Virus ◽

C Terminus ◽

Kinetics Of

Poxvirus interleukin (IL)-18 binding proteins (IL-18BPs) are soluble decoys that inhibit the activity of IL-18. The aim of this study was to demonstrate IL-18 binding activity of the Variola virus protein D7L. D7L effectively inhibited the biological activity of IL-18 in a bioassay. We compared the affinity and kinetics of D7L and the Ectromelia virus IL-18BP, p13, for human and murine IL-18 using surface plasmon resonance and no differences were detected, indicating that the differences in amino acid sequence did not affect binding or species specificity. Both proteins had higher affinity for murine than human IL-18. This was similar to human IL-18BP and the Molluscum contagiosum virus IL-18BP, which also demonstrated higher affinity for human IL-18. The host range of Variola virus is limited to humans and thus the affinity of D7L for IL-18 does not correlate with its host range. Furthermore, we demonstrated that D7L is capable of interacting with glycosaminoglycans (GAGs) via the C terminus, while p13 is not. Importantly, D7L interacted with both GAG and IL-18 simultaneously, indicating that the binding sites were distinct.

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