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H2020Individual fellowship2019–2020

HIV VCC Interference · Characterisation of single molecule dynamics within HIV-1 reservoirs as a target for interference with virus persistence and immune evasion

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2019-01-01 → 2020-12-31
EU contribution
€158,122
Participants
1
Scheme
MSCA-IF-EF-ST

Lines connect the coordinator with its partners.

Results in brief

Characterisation of single molecule dynamics within HIV-1 reservoirs as a target for interference with virus persistence and immune evasion

Human Immunodeficiency Virus type 1 (HIV-1) still remains a significant cause of illness and death around the world. One of the reasons HIV-1 infection is difficult to treat is the virus’s ability to create hidden reservoirs in cells. These virus reservoirs, termed Virus-Containing Compartments (VCCs) are inaccessible to the immune system and help to spread the infection to different parts of the body. Moreover, VCCs are unaffected by current HIV-1 therapies, and thus remain a major obstacle in the development of successful HIV-1 cure strategies. This project has utilized advanced fluorescence microscopy techniques to study the dynamic behaviour of lipid and protein molecules inside VCC membranes of living cells of the immune system infected with HIV-1. This behaviour was then compared to the behaviour of the same molecules on the cell surface. Results of this project have shown that VCCs exhibit a distinct behaviour of lipids inside VCC at the sites of interaction between individual viruses and cell membranes as compared to the rest of the cell membranes. The interference with this unique behaviour may thus be utilised to design a new type of a drug therapy that reduces the ability of immune cells to create virus reservoirs and results have shown that drugs that alter the behaviour of lipid membranes in cells appear to reduce the ability of infected cells to form VCCs. Overall, this project has utilised advanced microscopy techniques to improve the understanding of VCC characteristics and thus provide a possible future avenue for new therapies that target the issue of HIV-1 immune system avoidance and persistence in infected person’s body.

Data: CORDIS, © European Union

Project objective

Human Immunodeficiency Virus type 1 (HIV-1) remains a significant cause of comorbidity and mortality around the world. One of HIV-1 persistence and immune evasion mechanisms is the ability to create hidden virus reservoirs in cells. These virus reservoirs, termed Virus-Containing Compartments (VCCs) are inaccessible to the immune system and help to spread the infection to different parts of the body. VCCs are unaffected by current HIV-1 therapies, and thus remain a major obstacle in the development of successful HIV-1 cure strategies. This project will take a novel approach to the interference with this mechanism of HIV-1 persistence by characterising and exploiting unique molecular dynamics inside VCCs in dendritic cells. Cutting edge super-resolution microscopy techniques enable the study of single molecule behaviour and have already been employed to investigate the minute details of virus-cell interactions during HIV-1 assembly, entry and cell-to-cell spread. These interactions were shown to depend on a specific arrangement and mobility of virus and cell molecules suggesting that efficient virus sequestration and release from VCCs may also require a specific distribution and dynamics of interacting lipids and proteins. Specifically, the “HIV VCC Interference” project aims to: 1) characterise the distribution and dynamics of lipids and proteins in VCCs as a whole and at the sites of virus-cell interactions using super-resolution microscopy; 2) assess the unique characteristics of these sites as targets for interference with HIV-1 persistence and to explore the potential of these targets by testing drugs that perturb specific aspects of cell membranes. These studies, which are aligned with objectives of MSCA-IF, will lead to the description of novel single molecule details of VCC environments and the characterisation of a new type of HIV-1 therapy that targets virus persistence by interfering with unique membrane properties of virus reservoirs.

Original text from CORDIS.

Participants

  • FUNDACIO PRIVADA INSTITUT DE RECERCA SOBRE IMMUNOPATOLOGIES-CAIXA, IRSICAIXA · BarcelonaCoordinatorSpain

Links

Data: CORDIS, © European Union