Porcine, murine and human sialoadhesin (Sn/Siglec-1/CD169): portals for porcine reproductive and respiratory syndrome virus entry into target cells

Abstract

Porcine sialoadhesin (pSn; a sialic acid-binding lectin) and porcine CD163 (pCD163) are molecules that facilitate infectious entry of porcine reproductive and respiratory syndrome virus (PRRSV) into alveolar macrophages. In this study, it was shown that murine Sn (mSn) and human Sn (hSn), like pSn, can promote PRRSV infection of pCD163-expressing cells. Intact sialic acidbinding domains are crucial, since non-sialic acid-binding mutants of pSn, mSn and hSn did not promote infection. Endodomain-deletion mutants of pSn, mSn and hSn promoted PRRSV infection less efficiently, but also showed markedly reduced expression levels, making further research into the potential role of the Sn endodomain in PRRSV receptor activity necessary. These data further complement our knowledge on Sn as an important PRRSV receptor, and suggest -in combination with other published data -that species differences in the main PRRSV entry mediators Sn and CD163 do not account for the strict host species specificity displayed by the virus.The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major disease problems in the swine industry today. The virus specifically infects swine and there is currently no evidence that any other species is susceptible to PRRSV infection. Within its host, PRRSV shows a narrow cell tropism, with macrophages being major target cells (Duan et al., 1997a, b;Teifke et al., 2001). As transfection of the viral RNA genome in otherwise nonpermissive cells results in productive infection, it was postulated that the restricted cell tropism is linked with the presence of specific entry mediators in target cells (Kreutz, 1998;Meulenberg et al., 1998). PRRSV entry in alveolar macrophages has already been extensively studied and a number of entry mediators have been identified (Van Breedam et al., 2010a). Two of these molecules appear to be crucial for efficient infection of porcine alveolar macrophages: sialoadhesin (Sn/Siglec-1/CD169) and CD163. Sn mediates efficient binding and internalization of the virus (Delputte et al., 2007;Van Breedam et al., 2010b;Vanderheijden et al., 2003), whereas CD163 is most likely involved in genome release (Calvert et al., 2007;Van Gorp et al., 2008). For CD163, it was reported that not only the porcine variant of this protein, but also several homologues originating from other mammalian species, display a PRRSV entry mediator activity (Calvert et al., 2007). In addition, the CD163 endodomain was found to be dispensable for its functionality as a PRRSV entry mediator (Lee & Lee, 2010; Van Gorp et al., 2010). Although the PRRSV GP 2 and GP 4 glycoproteins were identified as potential interaction partners for CD163 (Das et al., 2010), the exact functioning of this molecule in PRRSV infection remains unclear. This stands in sharp contrast to our current knowledge on Sn. Ample data have shown that sialic acids on the virion surface interact with the Nterminal sialic acid-binding domain of Sn, upon which the virus-receptor complex is internalized via a process of clathrin...

Immortalized MH-S cells lack defining features of primary alveolar macrophages and do not support mouse pneumovirus replication

“…As highlighted in a recent review [48], cell surface Siglecs as a group interact with numerous pathogens and pathogen-derived ligands. Interestingly, the macrophage cell surface protein Siglec-1 (Sialoadhesin; CD169), was initially characterized as an important receptor for porcine reproductive and respiratory syndrome virus (PRRSV) [49] although a recent study that monitored PPRSV infection in Siglec-1 gene deleted pigs suggested modification of this hypothesis [50]. Siglec-1 interacts with retroviruses HIV and murine leukemia virus and mediates virion transfer to T lymphocytes [51, 52].…”

The Crystal Structure of the Fifth Scavenger Receptor Cysteine-Rich Domain of Porcine CD163 Reveals an Important Residue Involved in Porcine Reproductive and Respiratory Syndrome Virus Infection

“…Earlier studies showed that pCD163 cooperated with another putative receptor, porcine sialoadhesin (Sn/CD169) (23), to facilitate the PRRSV infection, where the former contributed to the uncoating of PRRSV while the latter promoted the attachment and internalization (invasion) of the virus (40)(41)(42)(43)(44)(45)(46)(47)(48). However, one study showed that Sn gene knockout pigs were infected by PRRSV as usual (49), and a recent study using geneedited pigs demonstrates the indispensability of pCD163 (28).…”

Emerging concepts in the pathogenesis of theStreptococcus pneumoniae: From nasopharyngeal colonizer to intracellular pathogen

“…CD169 (Siglec1/Sialoadhesin) is a lectin receptor that mediates uptake of sialylated bacteria and viruses by macrophages (Chang et al, ; Heikema et al, ; Klaas et al, ). These macrophages are known to be permissive for viral replication in mice and pigs due to their ineffective bactericidal mechanisms and higher expression levels of suppressors of cytokine signalling (Honke et al, ; Van Breedam, Verbeeck, Christiaens, Van Gorp, & Nauwynck, ). Using an ex vivo pig spleen perfusion model, they confirmed the role of CD169 + macrophages as a reservoir for intracellular replication of pneumococci within the spleen.…”