Expression of the C-type lectins DC-SIGN or L-SIGN alters host cell susceptibility for the avian coronavirus, infectious bronchitis virus
ABSTRACT Infectious bronchitis virus (IBV), an avian coronavirus, is a cause of great economic loss in the poultry industry. The virus mainly infects respiratory epithelium, but can be also detected in other organs. The functional receptor for the virus has not been found and field strains of IBV do not infect conventional cell lines. Recently, it has been shown that the C-type lectins DC-SIGN/L-SIGN can promote entry of several coronaviruses. Here we examine whether DC-SIGN/L-SIGN are entry determinants for IBV. We show that by introducing human DC-SIGN/L-SIGN into non-permissive cells, infection by the IBV is dramatically increased. DC-SIGN mediated infection was inhibited by mannan and anti-lectin antibodies, and was independent of sialic acid levels on the cell. Enhancement of IBV infection also occurred for different serotypes of IBV. Our findings demonstrated that even in the absence of avian-specific receptor, DC-SIGN-like lectins are capable of mediating efficient IBV infection.
Article: The avian coronavirus spike protein[Show abstract] [Hide abstract]
ABSTRACT: Avian coronaviruses of the genus Gammacoronavirus are represented by infectious bronchitis virus (IBV), the coronavirus of chicken. IBV causes a highly contagious disease affecting the respiratory tract and, depending on the strain, other tissues including the reproductive and urogenital tract. The control of IBV in the field is hampered by the many different strains circulating worldwide and the limited protection across strains due to serotype diversity. This diversity is believed to be due to the amino acid variation in the S1 domain of the major viral attachment protein spike. In the last years, much effort has been undertaken to address the role of the avian coronavirus spike protein in the various steps of the virus' live cycle. Various models have successfully been developed to elucidate the contribution of the spike in binding of the virus to cells, entry of cell culture cells and organ explants, and the in vivo tropism and pathogenesis. This review will give an overview of the literature on avian coronavirus spike proteins with particular focus on our recent studies on binding of recombinant soluble spike protein to chicken tissues. With this, we aim to summarize the current understanding on the avian coronavirus spike's contribution to host and tissue predilections, pathogenesis, as well as its role in therapeutic and protective interventions. Copyright © 2014 Elsevier B.V. All rights reserved.Virus Research 10/2014; 194. DOI:10.1016/j.virusres.2014.10.009 · 2.83 Impact Factor
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ABSTRACT: Abstract Chickens from two inbred lines selected for high (L10H) or low (L10L) mannose-binding lectin (MBL) serum concentrations were infected with infectious bronchitis virus (IBV), and innate as well as adaptive immunological parameters were measured throughout the experimental period. Chickens with high MBL serum concentrations were found to have less viral load in the trachea than chickens with low MBL serum concentrations indicating that these chickens were less severely affected by the infection. This study is the first to show that MBL expression is present in the lungs of healthy chickens and that the expression is upregulated at days 3 postinfection (p.i.) in L10H chickens. Furthermore, in the liver of infected chickens, the MBL expression was upregulated at day 7 p.i., despite the fact that the MBL serum concentrations were decreased below baseline at that time point. The number of TCRγδ+CD8α+ cells in the blood of noninfected chickens increased from week 0 to 3 p.i. However, the number of cells was higher in L10H chickens than in L10L chickens throughout the experiment. No increase was observed in the number of TCRγδ+CD8α+ cells in the blood of the infected L10H and L10L chickens. The numbers of B cells at week 3 p.i. were higher for noninfected L10L chickens than for the other chickens. No differences were observed between the infected and noninfected L10H chickens or between the infected L10H and L10L chickens. Furthermore, at week 3 p.i., the number of monocytes was higher in infected and noninfected L10H chickens than in the infected and noninfected L10L chickens. Thus, these results indicate that MBL is produced locally and may be involved in the regulation of the cellular immune response after an IBV infection. However, MBL did not appear to influence the humoral immune response after IBV infection in this study.Viral Immunology 10/2014; 27(10). DOI:10.1089/vim.2014.0088 · 1.64 Impact Factor
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ABSTRACT: Human coronavirus NL63 (HCoV-NL63) is an alphacoronavirus that was first identified in 2004 in the nasopharyngeal aspirate from a 7-month-old patient with a respiratory tract infection. Previous studies showed that HCoV-NL63 and the genetically distant SARS-CoV employ the same receptor for host cell entry, angiotensin converting enzyme 2 (ACE2), but it is largely unclear whether ACE2 interactions are sufficient to allow HCoV-NL63 binding to cells. The present study showed that directed expression of angiotensin-converting enzyme 2 (ACE2) on cells previously resistant to HCoV-NL63 renders them susceptible, showing that ACE2 protein acts as a functional receptor and its expression is required for infection. However, comparative analysis showed that directed expression or selective scission of the ACE2 protein had no measurable effect on virus adhesion. In contrast, binding of HCoV-NL63 to heparan sulfates was required for viral attachment and infection of target cells, showing that these molecules serve as attachment receptors for HCoV-NL63.Journal of Virology 09/2014; 88(22). DOI:10.1128/JVI.02078-14 · 4.65 Impact Factor