For example, sialylated N-glycans within the CRDs of human and porcine SP-A are recognized by the HA of susceptible IAV strains. Pentraxins are a phylogenetically ancient family of proteins characterized by a conserved pentameric structure comprised of five identical non-covalently linked subunits. PTX3, the prototype of the long pentraxins, and the short pentraxins SAP and Creactive Navitoclax proteinhave been proposed to play important roles in innate immunity and inflammation via modulation of complement activation, pathogen recognition and clearance of apoptotic cells. PTX3, SAP and CRP have been reported to bind to a variety of pathogens, however relatively little is known regarding their role in antiviral host defence. We recently demonstrated that the long pentraxin PTX3 acts as a c-type inhibitor of IAV. To gain further insight regarding the antiIAV activities of pentraxins, we compared short pentraxinsand the long pentraxin PTX3 for their ability to bind and inhibit different strains of IAV. In contrast to previous studies indicating that SAP mediated anti-IAV activity in a manner characteristic of b-type inhibitors, our preliminary studies demonstrated that lectin-mediated binding of SAP to IAV was not a critical determinant of its anti-IAV activity. Herein, we demonstrate that SAP expresses a-linked sialylated glycans and acts as a classical c inhibitor of IAV. Moreover, we have selected and characterized IAV mutants resistant to the antiviral activities of SAP, thereby defining amino acid residues critical to the interactions between SAP and susceptible IAV strains. Unlike SAP and PTX3, the related pentraxin CRP is generally not glycosylated, consistent with our inability to detect binding or HI activity against any of the IAV strains tested. Glycosylated molecular variants of human CRP are, however, induced in some pathological conditionsand show distinct patterns of binding to serum glycoproteins when compared to the non-glycosylated protein. Glycosylated variants of CRP differed not only in SA content but also in linkage specificity to sub-terminal sugars and variants Talazoparib expressing a- or a-linked SA were induced in response to different disease conditions. CRP used in our studies was purified from human serum, however it will be of interest to determine if CRP is also present in airway fluids and, if so, to analyze its glycosylation status during IAV infection and/or pulmonary inflammation. The sialylated diantennary glycan expressed by SAP does not display the microheterogeneity characteristic of many mammalian glycoproteinsand although its function is not fully understood it has been proposed to be involved in pentamer-pentamer associations. In contrast, PTX3 preparations from different cell types show heterogeneity in the relative amounts of bi, tri and tetrantennary glycans and removal of SA from PTX3 potentiates its ability to bind certain ligands such as C1q. Therapeutic treatment of mice with human SAP has been shown to attenuate fibrotic lung diseaseand fungal sporeinduced allergic airway disease. However, limitations associated with the mouse model of IAV infection have made it difficult to clearly define the in vivo role of SAP during IAV infections. For example, mice are not naturally infected with IAV and passage of human isolates through mouse lung selects for mutants with greater replication efficiency. As such, mouseadapted IAV generally bind a-linked SA, the predominant linkage expressed in the 
murine respiratory tractcompared to human strains which display HA receptor preference for alinked SA which is widely expressed by epithelial cells in the upper human airways. Not surprisingly, mice deficient in murine SAP but transgenic for human SAP did not show enhanced susceptibility to PR8.