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.
"According to various reports, DC-specific C type lectin DC-SIGN is an important attachment factor for dissemination of several pathogens. As viral attachment factors, DC-SIGN (R) can enhance the susceptibility of permissive cells to viral infection or allow non-permissive cells to bind and transmit captured pathogens to target cells in trans (Halary et al., 2002; Navarro-Sanchez et al., 2003; Borggren et al., 2012; Mesman et al., 2012; Zhang et al., 2012). These attachment factors have high affinity for the mannose containing carbohydrates on viral glycoproteins (Klimstra et al., 2003; Lin et al., 2003; Johnson et al 2011; Alen et al., 2012). "
"For avian gammacoronaviruses, no such protein receptor has been elucidated, but alpha-2,3 linked sialic acids have been shown to be essential for attachment and subsequent infection of avian cells (Abd El Rahman et al., 2009; Wickramasinghe et al., 2011; Winter et al., 2006, 2008). In addition, it was recently demonstrated that expression of human DC-SIGNlike lectins renders cells susceptible to IBV infection (Zhang et al., 2012), but no avian counterpart of this molecule has yet been identified . Thus, the molecular determinants for the host and tissue range of IBV are yet far from understood. "
[Show abstract][Hide abstract] ABSTRACT: The spike protein is the major viral attachment protein of the avian coronavirus infectious bronchitis virus (IBV) and ultimately determines viral tropism. The S1 subunit of the spike is assumed to be required for virus attachment. However, we have previously shown that this domain of the embryo- and cell culture adapted Beaudette strain, in contrast to that of the virulent M41 strain, is not sufficient for binding to chicken trachea (Wickramasinghe et al., 2011). In the present study, we demonstrated that the lack of binding of Beaudette S1 was not due to absence of virus receptors on this tissue nor due to the production of S1 from mammalian cells, as S1 proteins expressed from chicken cells also lacked the ability to bind IBV-susceptible embryonic tissue. Subsequently, we addressed the contribution of the S2 subunit of the spike in IBV attachment. Recombinant IBV Beaudette spike ectodomains, comprising the entire S1 domain and the S2 ectodomain, were expressed and analyzed for binding to susceptible embryonic chorio-allantoic membrane (CAM) in our previously developed spike histochemistry assay. We observed that extension of the S1 domain with the S2 subunit of the Beaudette spike was sufficient to gain binding to CAM. A previously suggested heparin sulfate binding site in Beaudette S2 was not required for the observed binding to CAM, while sialic acids on the host tissues were essential for the attachment. To further elucidate the role of S2 the spike ectodomains of virulent IBV M41 and chimeras of M41 and Beaudette were analyzed for their binding to CAM, chicken trachea and mammalian cell lines. While the M41 spike ectodomain showed increased attachment to both CAM and chicken trachea, no binding to mammalian cells was observed. In contrast, Beaudette spike ectodomain had relatively weak ability to bind to chicken trachea, but displayed marked extended host range to mammalian cells. Binding patterns of chimeric spike ectodomains to these tissues and cells indicate that S2 subunits most likely do not contain an additional independent receptor-binding site. Rather, the interplay between S1 and S2 subunits of spikes from the same viral origin might finally determine the avidity and specificity of virus attachment and thus viral host range.
Virus Research 09/2013; 177(2). DOI:10.1016/j.virusres.2013.09.006 · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes-A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.
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