Three lines of evidence identify Siglec-1 as a novel DC receptor for HIV-1 capture and trans-infection: (i) Siglec-1 expression correlates with viral capture and trans-infection capacity of DCs, (ii) mAbs against Siglec-1 specifically inhibit HIV-1 capture in a dose-dependent manner, and (iii) SIGLEC1 knockdown reduces viral capture and trans-infection, while heterologous de novo expression of Siglec-1 enhances HIV-1 capture and trans-infection. The gene discussed is SIGLEC1; the disease is infection.