Impact of KIR and HLA genotypes on the outcome and susceptibility to Ebola virus disease
|Title :||Impact of KIR and HLA genotypes on the outcome and susceptibility to Ebola virus disease|
|Translated title :||[fr] L'impact des génotypes KIR et HLA sur l'issue et la susceptibilité de la maladie à virus Ebola|
|Author :||Lhermitte, Valentine|
|Date of defense :||27-Aug-2018|
|Advisor(s) :||Willems, Luc
|Committee's member(s) :||Sindic, Marianne
|Number of pages :||71|
|Keywords :||[en] KIR|
|Discipline(s) :||Life sciences > Biochemistry, biophysics & molecular biology|
|Research unit :||Rega Institute, KU Leuven|
|Target public :||Researchers|
Professionals of domain
|Institution(s) :||Université de Liège, Liège, Belgique|
|Degree:||Master en bioingénieur : chimie et bioindustries, à finalité spécialisée|
|Faculty:||Master thesis of the Gembloux Agro-Bio Tech (GxABT)|
[en] Ebola virus (EBOV) induces a zoonotic disease with a high fatality rate, which affects human and non-human primates. First appeared in 1976, the Ebola Virus Disease (EVD) continues to take a lot of people life, mainly in Africa where the health infrastructures are poor, weak and not adapted. The 2014-2016 EBOV outbreak in West Africa was the largest and the most complex outbreak since its apparition. A better understanding of ebolavirus, the development of innovative treatments and the discovery of an efficient EBOV vaccine could help to prevent future EBOV outbreaks and the spread of this life-threatening infection.
EBOV carries a negative-sense RNA genome and has glycoprotein spikes, which are very important for the virus entry into host cells. The envelope, the matrix and the nucleocapsid are also components of this virion, and can be recognized by the innate and adaptive immune cells.
Natural Killer (NK) cells are among the important components of the innate immune system and provide the first line of defense against infected and transformed cells. They own activating and inhibitory receptors on their membrane in order to induce an appropriate innate immune response. Killer Immunoglobulin-like Receptors (KIRs) are one of the main receptors of NK cells. Human Leucocyte Antigen (HLA) class I molecules are located on nucleic cell membrane and are the KIR proteins ligands. Some combinations of KIR and HLA molecules could influence the susceptibility and outcome of several viral infections.
The objective of this master’s thesis is to assess the association of KIR and HLA genotypes with EVD outcome by comparing the genotypes of different groups of patients: contacts, survivors and fatalities of EVD.
Results show that some KIR and HLA combinations correlate with the outcome of EVD. First, these KIR combinations “2DL1-4, 2DS4-001/3, 3DL1-3, 2DP1 and 3DP1-004”, “2DL1-4, 2DS4-001, 3DL1-3, 2DP1 and 3DP1-004” and the last one “2DL1-5, 2DS1-3, 2DS4-001, 3DL1-3, 2DP1 and 3DP1-004” and these HLA combinations “HLA-C1” and “HLA-C1/2 and HLA-B-Bw4Ile” might provide a permissive immune microenvironment promoting a positive outcome of EVD. Secondly, survivors tend to own less activating KIR, which can confer a protection against EVD. Finally, KIR2DS4-003 and KIR2DS2 might increase the susceptibility to develop a fatal EVD.
These results highlight the fact that KIR and HLA genes may play a key role in the susceptibility and outcome of some viral infections and especially EVD.
Cite this master thesis
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