Characterisation of HIV-1 infection of immune cells
Research type
Research Study
Full title
Characterisation of HIV-1 infection of immune cells
IRAS ID
229855
Contact name
Q Sattentau
Contact email
Sponsor organisation
University of Oxford
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
2 years, 1 months, 28 days
Research summary
The aims of this project are two-fold. Firstly, to investigate the signals involved in uptake of HIV-1-infected T cells by macrophages. Secondly, to study the effects of HIV-1 infection on monocyte/macrophage activation and trafficking. The results of the study will help to shed light on the mechanism of establishment of the macrophage reservoir and HIV-1 dissemination in vivo and provide potential targets for anti-inflammatory therapies adjunctive to antiretroviral therapy.
To achieve this blood will be taken from healthy volunteers recruited from the University of Oxford by department-wide email lists by a trained member of staff following acquisition of informed consent. In addition blood will also be obtained from the NHSBT, which already has informed consent for use of these samples in research. Once acquired, the blood will be anonymised and processed to obtain the peripheral blood mononuclear cells (PBMCs). These cells will then be cultured and infected and analysed to address the questions described above.
This work has been reviewed and funded by the Wellcome Trust Infection, Immunity and Translational Medicine PhD program and the Edward P Abraham Trust PhD program.Lay summary of study results: Billions of dying cells are cleared by the body every day, both during health and in disease, such as during viral (eg. HIV-1 and SARS CoV-2) infections. Defects in the clearance of dying cells leads to unwanted inflammation which drives diseases such as autoimmunity, cardiovascular disease, neurodegeneration and cancer. Therefore, understanding how body removes dead cells and how this can fail is important for preventing and treating these diseases. In our laboratory work we used human lymphocytes derived from the blood of healthy people to probe the mechanisms by which dying cells are cleared by the body's scavenger cells called macrophages. We found that the carbohydrate coating on the surface of all human cells called the glycocalyx, which protects them from unwanted scavenging by macrophages, is cleared during cell death. This allows macrophages to capture and digest the dying cells, therefore preventing deleterioius inflammation. In summary, our in vitro work with human blood cells has allowed us to solve a question central to the avoidance of unhealthy inflammation in the body, and may lead to potential treatments relating to unwanted inflammatory disease.
REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
17/WM/0333
Date of REC Opinion
22 Aug 2017
REC opinion
Favourable Opinion