Figure 2.

Models for CLR‐mediated enhancement of IAV infection. (A) IAV infection of SA‐deficient Lec2 CHO cells via CLR. (i) Lectin‐mediated binding of the DC‐SIGN CRD (shown in blue) to mannose‐rich glycans on IAV HA/NA could lead to direct DC‐SIGN‐mediated endocytosis. Alternatively, (ii) IAV could be passed from DC‐SIGN to additional cell‐surface receptor(s) (the identity of which is currently unknown; shown in green), resulting in enhanced infection of Lec2 cells. Note that CLRs could also remain associated with IAV to facilitate entry via additional coreceptors. (B) IAV infection of MΦ and DC: a multistep process involving CLRs. (i) IAV HA binds to SA on cell‐surface glycoproteins or glycolipids. Abundant cell‐surface SA provides multiple sites for IAV attachment, thereby concentrating IAV at the cell surface. (ii) Attachment to cell‐surface SA facilitates lectin‐mediated binding of CLRs to glycans on IAV HA/NA. Lectin‐mediated binding may be strengthened by HA‐mediated recognition of SA residues expressed on CLRs. Direct CLR‐mediated entry may result, or (iii) CLRs may pass IAV to additional unidentified receptor(s) (shown in green) for virus entry. Binding of IAV to additional receptors could be SA‐dependent or ‐independent. Interactions between IAV and unidentified receptors could also occur independently of CLRs [i.e., Step (i) followed by Step (iii)]. In addition, IAV could be endocytosed directly after binding to sialylated receptors in Step (i).