Role of dendritic cells in HIV response

Role of dendritic cells in HIV response

Project

Dentritic cells play an important role in the immune system. As soon as a pathogen invades the body, dentritic cells activate the immune system. This does not occur with HIV. There are indications, however, that an immune response is induced after certain proteins have been suppressed. AMC researcher, Sonja Gringhuis, aims to determine what actually happens when these proteins are suppressed and what the mechanism is that uses the HIV virus to evade dentritic cells.

Project details

Time frame
31 December 2012 - 04 February 2017
Budget
€ 250,000
Active in
Netherlands

Objectives

Here we will identify the molecular mechanisms induced by HIV-1 to escape antiviral immunity in dendritic cells, identify the putative HIV-1 sensor involved and how we can harness this knowledge to induce antiviral immunity in DCs to prevent HIV-1 replication and induce apoptosis of infected cells.

We hypothesize that HIV-1 requires Raf-1 signaling to escape activation of a novel HIV-1 sensor preventing immune activation and apoptosis and we will investigate:
Objective 1. Antiviral responses, immune activation and apoptosis after HIV-1 infection.
Objective 2. Mechanism of HIV-1 sensing and antiviral immune activation.
Objective 3. Harnessing antiviral immunity for vaccine development and apoptosis induction for elimination of HIV-1 reservoirs

This could lead to new information that could fuel (therapeutic) vaccin development

Community groups

scientific community

Background

Type I interferon is a crucial component of antiviral defense. Most cells have intrinsic sensors of nucleic acids that detect viral infections and subsequently trigger interferon responses to combat such infections. Strikingly, infection of dendritic cells (DCs), T cells and macrophages with HIV-1 does not induce antiviral interferon responses. How HIV-1 avoids triggering the viral sensors is an open question.

Little is known about intrinsic HIV-1 sensors. Recent studies have indicated the presence of a DNA sensor against HIV-1 as well as a cryptic sensor induced by newly synthesized capsid/Cyclophilin A complexes. Our novel data strongly suggest that there the Raf-1 signaling pathway masks an unknown HIV-1 sensor. We have previously shown that HIV-1 uses pattern recognition receptors DC-SIGN and TLR8 for its replication in DCs. Thus, recent studies strongly suggest that HIV-1 evades viral recognition through different mechanisms.

Goals

< 200,000 new HIV infections globally
33%
Contributed within this project
A cure for HIV
66%
Contributed within this project

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