Interaction of Decay-Accelerating Factor with Coxsackievirus B3

Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, IN 47907-2054, USA.
Journal of Virology (Impact Factor: 4.44). 01/2008; 81(23):12927-35. DOI: 10.1128/JVI.00931-07
Source: PubMed


Many entero-, parecho-, and rhinoviruses use immunoglobulin (Ig)-like receptors that bind into the viral canyon and are required
to initiate viral uncoating during infection. However, some of these viruses use an alternative or additional receptor that
binds outside the canyon. Both the coxsackievirus-adenovirus receptor (CAR), an Ig-like molecule that binds into the viral
canyon, and decay-accelerating factor (DAF) have been identified as cellular receptors for coxsackievirus B3 (CVB3). A cryoelectron
microscopy reconstruction of a variant of CVB3 complexed with DAF shows full occupancy of the DAF receptor in each of 60 binding
sites. The DAF molecule bridges the canyon, blocking the CAR binding site and causing the two receptors to compete with one
another. The binding site of DAF on CVB3 differs from the binding site of DAF on the surface of echoviruses, suggesting independent
evolutionary processes.

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Available from: Valorie D Bowman
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    • "A subset of CV-B also attaches to an accessory receptor called DAF (or CD55). DAF is a 70-KDa glycosylphosphatidylinositol-linked complement regulatory protein consisting of four extracellular short consensus repeats (SCR) [11] [12]. DAF protects autologous cells from attack by complement proteins [13] and its expression on the cell surface is almost ubiquitous throughout the human body. "
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    ABSTRACT: A subset of coxsackieviruses B (CV-B) is able to initiate intestinal infection via the attachment to two cell surface proteins, decayaccelerating factor (DAF) and coxsackie adenovirus receptor (CAR). The aim of the present study was to investigate the expression pattern of these receptors in the polarized CaCo-2 cell line using flow cytometry. The expression of CAR-specific mRNA and proteins was analyzed by reverse transcriptase polymerase chain reaction and western blotting, respectively. Flow cytometry analysis was used to study the surface expression patterns of CAR and DAF. CAR and DAF were well detected at the surface of CaCo-2 cells by flow cytometry. Despite the fact that CAR was susceptible to the action of trypsin, a few amounts of the latter enzyme and a precise dilution did not impair its correct detection by flow cytometry. This technique was used to demonstrate that the density of cells did not influence the expression of CAR at the cell surface. CaCo-2 cells express high levels of CAR and DAF at their surface. Flow cytometry, if used adequately, represents a helpful tool for the study of the interactions between these cells and various viral targets.
    Full-text · Article · Jul 2014 · Central European Journal of Biology
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    • "Additionally, CV-B serotypes 1, 3, and 5 have been found to bind Decay-Accelerating Factor (DAF/CD55) as a co-receptor [9,15-17]. DAF, a 70 kDa glycosylphosphatidylinositol-anchored membrane protein, is a member of the regulators of complement activation (RCA) family that regulate complement activation by binding to and accelerating the decay of convertases, the central amplification enzymes of the complement cascade [18]. DAF functional region consists of four short consensus repeats (SCR1 to 4) [16,17,19]. "
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    ABSTRACT: Background Decay Accelerating Factor (DAF) and Coxsackievirus-Adenovirus Receptor (CAR) have been identified as cellular receptors for Coxsackie B viruses (CV-B). The aim of this study is to elucidate the different binding properties of CV-B serotypes and to find out if there are any amino acid changes that could be associated to the different phenotypes. Twenty clinical CV-B isolates were tested on CaCo-2 cell line using anti-DAF (BRIC216) and anti-CAR (RmcB) antibodies. CV-B3 Nancy prototype strain and a recombinant strain (Rec, CV-B3/B4) were tested in parallel. The P1 genomic region of 12 CV-B isolates from different serotypes was sequenced and the Trans-Epithelial Electrical Resistance (TEER) along with the virus growth cycle was measured. Results Infectivity assays revealed clear differences between CV-B isolates with regard to their interactions with DAF and CAR. All tested CV-B isolates showed an absolute requirement for CAR but varied in their binding to DAF. We also reported that for some isolates of CV-B, DAF attachment was not adapted. Genetic analysis of the P1 region detected multiple differences in the deduced amino acid sequences. Conclusion Within a given serotype, variations exist in the capacity of virus isolates to bind to specific receptors, and variants with different additional ligands may arise during infection in humans as well as in tissue culture.
    Full-text · Article · May 2014 · Journal of Biomedical Science
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    • "within the known CAR-binding footprint of CVB3 and four of the mutations detected in CVB1Nm mapped within or adjacent to the DAF footprint. Therefore, plaque-reduction assays using CVB1N, CVB1Nm, CVB3 (positive control) alone, or pre-incubated with either soluble hCAR or DAF were performed to characterize receptor usage [Hafenstein et al., 2007]. More than 2-log reductions in plaque number were observed when each virus was pre-incubated with soluble hCAR compared to virus alone (Table II, P < 0.05). "
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    ABSTRACT: To understand better how different genomic regions may confer pathogenicity for the coxsackievirus B (CVB), two intratypic CVB1 variants, and a number of recombinant viruses were studied. Sequencing analysis showed 23 nucleotide changes between the parental non-pathogenic CVB1N and the pathogenic CVB1Nm. Mutations present in CVB1Nm were more conserved than those in CVB1N when compared to other CVB sequences. Inoculation in C3H/HeJ mice showed that the P1 region is critical for pathogenicity in murine pancreas and heart. The molecular determinants of disease for these organs partially overlap. Several P1 region amino acid differences appear to be located in the decay-accelerating factor (DAF) footprint CVBs. CVB1N and CVB1Nm interacted with human CAR, but only CVB1N seemed to interact with human DAF, as determined using soluble receptors in a plaque-reduction assay. However, the murine homolog Daf-1 did not interact with any virus assessed by hemagglutination. The results of this study suggest that an unknown receptor interaction with the virus play an important role in the pathogenicity of CVB1Nm. Further in vivo studies may clarify this issue.
    Full-text · Article · Sep 2011 · Journal of Medical Virology
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