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Deciphering host genetics and viral determinants of MPOX epidemiology in the Democratic Republic of Congo

Project description

Unravelling the mysteries of monkeypox

Monkeypox, a virus related to smallpox, has seen a rise in cases beyond its usual African endemic regions, with recent transmission linked to sexual contact. However, not everyone exposed to the virus develops severe symptoms or falls ill. The EU-funded DECIPHER-MPOX project aims to understand why. Focusing on the Kamituga area in South Kivu, DRC, researchers will investigate host genetic and viral factors that influence disease outcomes. By analysing family cohorts and conducting genetic, transcriptomic, and immune profile studies, the project hopes to uncover determinants of susceptibility and protection, potentially guiding future vaccine strategies.

Objective

Background: Monkeypox virus (MPV) is a member of the Poxviridae family that includes smallpox, cowpox and chickenpox viruses. Endemic to equatorial Africa following casual human to animal or human to human transmission , recent events have seen an increased incidence with indications of sexual transmission. The disease is characterized by fever, muscle aches, skin rash, lymphadenopathy, oral sores, sore throat, cough, etc. Within any cluster of high risk contacts of a case mpox; however, not everyone exposed develops clinical disease. Moreover, among those contacts who develop mpox, not everyone gets severe disease or dies.
Hypothesis: Host genetic & viral factors explain the differential outcomes following exposure to MPV.
Objectives: To determine the host genetic and viral determinants of mpox disease in Kamituga area, South Kivu province, DRC. Specifically, we will (I) establish well phenotyped cohorts of house-hold contacts, (II) determine rare variants via family trios; (III) undertake RNASeq for transcriptomics, and (IV) study differential cellular immunity profiles using digital cell sorting (DCS) , (V) identify viral variants that drive severe disease
Methods: Whole exome sequencing (WES), transcriptomics and DCS studies of house-family contacts clinically prequalified by PCR and serological testing. Virus gDNA will be reverse transcribed from sequenced host RNA and characterized by comparative genomics and phylogeny.
Potential impact: This project will elucidate host genetic & viral determinants of susceptibility to mpox disease in context of natural exposure and infection; that may serve as correlates of immune protection following vaccination.

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Programme(s)

Coordinator

NATIONAL HEALTH LABORATORY SERVICES
Net EU contribution
€ 156 750,00
Address
MODDERFONTEIN ROAD 1 GAUTENG
2131 Sandringham
South Africa

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Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 156 750,00

Participants (6)