CD169-mediated trafficking of HIV to plasma membrane invaginations in dendritic cells attenuates efficacy of anti-gp120 broadly neutralizing antibodies

PLoS Pathogens
Hisashi AkiyamaSuryaram Gummuluru

Abstract

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 NIH...Continue Reading

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Citations

Dec 7, 2017·Frontiers in Immunology·Yan-Cun LiuSong-Tao Shou
Dec 7, 2017·Frontiers in Immunology·Javier Martinez-PicadoNuria Izquierdo-Useros
Aug 11, 2017·Journal of Virology·Hisashi AkiyamaSuryaram Gummuluru
Apr 21, 2017·Journal of Virology·Caitlin M MillerSuryaram Gummuluru
Mar 5, 2016·Microbiology and Molecular Biology Reviews : MMBR·Helena M van DongenD Michiel Pegtel
Aug 29, 2018·Nature Communications·Hisashi AkiyamaSuryaram Gummuluru
Oct 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Nicolas RuffinPhilippe Benaroch
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Methods Mentioned

BETA
flow cytometry
super resolution microscopy
electron
super-resolution microscopy
electron microscopy
FACS
PCR
transfection
transfections
ELISA

Software Mentioned

GraphPad Prism
ImageJ
SoftWoRx
FPALM

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