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Evaluating Env-specific antibodies for the diagnosis and treatment of complex human diseases

Project description

The impact of HERV Env-specific antibodies on complex diseases

Human endogenous retroviruses (HERVs) are remnants of past viral infections, with abnormal HERV envelope (Env) proteins linked to cancer, autoimmune diseases, and infections. However, their exact role and prognostic value remain unclear. Supported by the Marie Skłodowska-Curie Actions programme, the ENVISAGE project will develop a platform to screen for HERV Env-specific antibodies and identify HERV insertions producing these proteins. It will generate HEK293T cell lines to measure antibody levels in cancer and autoimmune disease patients, while taking demographic factors into account. The project will also establish a pan-genome reference for HERV sequences, use targeted sequencing to identify active insertions, and analyse public datasets to assess the impact of HERV Env expression on disease progression.

Objective

Human endogenous retroviruses (HERV) are highly repetitive sequences that are remnants of viral infections successfully integrated in the genome. Aberrant expression of HERV envelope (Env) proteins is frequent in cancer, autoimmunity, neurodegeneration, and infection and has been associated with antibody responses. However, we do not know if all HERV Env proteins contribute to antibody responses or what the prognostic impact of HERV Env-specific antibodies is. Thus, the objectives of this proposal are to i) implement a high-throughput screening platform for HERV Env-specific antibodies and ii) develop a bioinformatics approach to identify the HERV insertions producing Env proteins. To achieve these goals, HEK293T cell lines overexpressing 10 different HERV Env proteins will be generated and used to quantify the abundance of Env-specific antibodies in serum from thousands of cancer, autoimmunity, and infection patients. With this work, we will determine if antibody responses to Env proteins are disease-specific and evaluate the impact of sex, age, and ethnicity on Env antibody titres. Following this, we will build a pangenome reference of HERV sequences in the human population to evaluate the polymorphism of HERV insertions. This database of HERV insertions will be used in combination with highly targeted sequencing (Amplicon-seq) and epigenomics to precisely identify the HERV insertions that are active in pathologies and produce Env proteins. Finally, we will analyse publicly available datasets to evaluate the impact of HERV Env expression on disease progression and survival. In addition to deepening our understanding of several human pathologies, this work could have important impacts on the diagnosis and treatment of complex human diseases.t

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

THE FRANCIS CRICK INSTITUTE LIMITED
Net EU contribution
€ 260 347,92
Address
1 MIDLAND ROAD
NW1 1AT London
United Kingdom
Region
London Inner London — West Camden and City of London
Activity type
Research Organisations
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Total cost
No data