CD169-Mediated Trafficking of HIV to Plasma Membrane Invaginations in Dendritic Cells Attenuates Efficacy of Anti-gp120 Broadly Neutralizing Antibodies

Myeloid dendritic cells (dcs) can capture hiv-1 via the receptor cd169/siglec-1 that binds to the ganglioside,gm3,in the virus particle membrane. in turn,hiv-1 particles captured by cd169,an i-type lectin,whose expression on dcs is enhanced upon maturation with lps,are protected from degradation in cd169+ virus-containing compartments (vccs) and disseminated to cd4+ t cells,a mechanism of dc-mediated hiv-1 trans-infection. in this study,we describe the mechanism of vcc formation and its role in immune evasion mechanisms of hiv-1. we find hiv-1-induced formation of vccs is restricted to myeloid cells,and that the cytoplasmic tail of cd169 is dispensable for hiv-1 trafficking and retention within vccs and subsequent trans-infection to cd4+ t cells. interestingly,introduction of a di-aromatic endocytic motif in the cytoplasmic tail of cd169 that results in endocytosis of hiv-1 particles,suppressed cd169-mediated hiv-1 trans-infection. furthermore,super-resolution microscopy revealed close association of cd169 and hiv-1 particles in surface-accessible but deep plasma membrane invaginations. intriguingly,hiv-1 particles in deep vccs were inefficiently accessed by anti-gp120 broadly neutralizing antibodies,vrc01 and nih45-46 g54w,and thus were less susceptible to neutralization. our study suggests that hiv-1 capture by cd169 can provide virus evasion from both innate (phagocytosis) and adaptive immune responses. © 2015 akiyama et al.