Figure 2.

Role of Siglec-1 in DC infection and antigen presentation. (A) Top: Siglec-1 facilitates HIV-1 infection of antigen presenting cells (APCs). In most DC subtypes, however, the restriction factor SAMHD1 inhibits reverse transcription, thus precluding immune sensing and the synthesis of viral antigens. Bottom: Conversely, HIV-2 encodes Vpx, which counteracts SAMHD1 activity allowing reverse transcription of the viral genome, that can be sensed via cGAs and trigger cytokine release. Newly synthesized proteins lead to the production of viral particles, but also to proteosomal cleavage and viral antigen presentation to CD8⁺ T cells via major histocompatibility complex class I (MHC)-I. (B) EBOV employs different receptors to attach to target cells, including CLRs, TIM/TAM receptors, and Siglec-1. Upon internalization, EBOV is directed to late endosomes and interacts with NPC1 receptor after being processed by cell cathepsins. In the cytoplasm, EBOV replicates producing new viral proteins and synthesized virions bud. While solid arrows indicate established mechanisms, dotted arrows suggest processes that require further investigation. vRNA: viral RNA; vDNA: viral DNA; SAMHD1: sterile alpha motif (SAM) domain- and histidine-aspartate (HD) domain-containing protein 1; cGAS: cyclic GMP-AMP synthase; TCR: T cell receptor; CLRs: C-type lectin receptors; TIM: T cell immunoglobulin and mucin domain receptor; TAM: Tyro-Axl-Mer receptor; CTSB: cathepsin B; NPC1: Nieman–Pick C1 receptor.