CD169-Mediated Trafficking of HIV to Plasma Membrane Invaginations in Dendritic Cells Attenuates Efficacy of Anti-GP120 Broadly Neutralizing Antibodies
PLoS Pathogens 2015, 11, 3
Dendritic cells (DCs) play a crucial role in eliciting adaptive immunity to pathogen infection. Certain pathogens such as the HIV virus have been shown to hijack DCs and use them to spread the virus to T cells, a mechanism known as trans-infection. This is thought to be mediated by the CD169 surface receptors on DCs, which capture the HIV virus and form virus containing compartments (VCCs). Broadly, the goal of this paper is to understand the mechanism of VCC formation and how the HIV virus utilizes VCCs to evade the immune system.
Single molecule 3D super-resolution microscopy was used to study the degree of association of CD169 and HIV-1 particles. The HIV-1 p24 gag protein was labeled with Cy3B and CD169 with Alexa 647. Two color 3D z-stacks were acquired to create a three-dimensional image of CD169 and HIV-1 interaction which showed a close association of the two entities in VCCs at the cell periphery about ~800 nm to 1 µm deep from the cell surface. Electron microscopy images corroborated results obtained with super-resolution microscopy.
In summary, the results indicate that VCCs are surface accessible but have a considerable invagination due to which the captured virus particles are protected from anti-gp120 broadly neutralizing antibodies. The interaction of HIV-1 particles with CD169 receptors could thereby protect the HIV virus from phagocytic degradation and anti-viral neutralization.
Personally, what stood out in the paper for me was how 3D super-resolution microscopy made it possible to obtain a high resolution snapshot of how the HIV-1 particles interact with CD169 receptors. Being able to show that they are co-localized (but not endocytosed) close to the surface of the cell in an invagination (pocket) that protects the virus from being degraded is a crucial piece of the puzzle.
