Ultra-high throughput analysis of immunoglobulin repertoires in acute HIV infection before and after initiation of antiretroviral therapy

PROJECT OVERVIEW 

There is currently no cure for HIV infection. Antiretroviral therapy (or 'ART') can prevent disease progression and has revolutionised the management of HIV infection. Although ART is not a cure, there are a growing number of cases of individuals who have started ART very early in HIV infection and then have stopped treatment, but with no evidence of the virus coming back. This phenomenon of post-treatment control (or 'PTC') has attracted much interest and may help provide key insights into how to cure HIV. In this study, we will analyse the effects of acute HIV infection and rapid initiation of antiretroviral therapy on the broader immunoglobulin repertoire. This study will take advantage of a bespoke microfluidics platform with which the supervisors have developed a workflow to sequence paired immunoglobulin heavy and light chain genes for hundreds of thousands to millions of B cells in a single blood sample.

KEYWORDS 

HIV, immunology, immune repertoire, bioinformatics, microfluidics

TRAINING OPPORTUNITIES 

Microfluidics, flow cytometry, fluorescence-activated cell sorting, bioinformatics, molecular biology 

KEY PUBLICATIONS 

1. Martin GE.... Frater J. Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy. Front Immunol. 2021 Jun 4;12:647688. doi: 10.3389/fimmu.2021.647688. PMID: 34149690; PMCID: PMC8213372.
2. Frater J, .... Oxford COVID Vaccine Trial Group. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial. Lancet HIV. 2021 Jun 18:S2352-3018(21)00103-X. doi: 10.1016/S2352-3018(21)00103-X. Epub ahead of print. PMID: 34153264; PMCID: PMC8213361.
3. Jones M... Frater J. Low copy target detection by Droplet Digital PCR through application of a novel open access bioinformatic pipeline, 'definetherain'. J Virol Methods. 2014 Jun;202(100):46-53. doi: 10.1016/j.jviromet.2014.02.020. Epub 2014 Mar 2. PMID: 24598230; PMCID: PMC4003534.
4. Laidlaw SM...Dustin LB. Tumor Necrosis Factor Inhibits Spread of Hepatitis C Virus Among Liver Cells, Independent From Interferons. Gastroenterology. 2017 Aug;153(2):566-578.e5. doi: 10.1053/j.gastro.2017.04.021. Epub 2017 Apr 26. PMID: 28456632; PMCID: PMC5627365.
5. Charles ED... Dustin LB. Somatic hypermutations confer rheumatoid factor activity in hepatitis C virus-associated mixed cryoglobulinemia. Arthritis Rheum. 2013 Sep;65(9):2430-40. doi: 10.1002/art.38041. PMID: 23754128; PMCID: PMC4026862.

KEY THEMES 

Immunology, infectious disease, HIV, bioinformatics