MOLECULAR EVOLUTION OF A NEW EBOLA VIRUS STRAIN AND ANALYSIS OF KIR GENE VARIANTS IN EBOLA VIRUS DISEASE

Ebolaviruses are emerging viruses that pose a significant threat to wildlife populations and to public health in Africa. Of the six viral species of the genus Ebolavirus, three can cause severe and fatal diseases in humans: Zaire ebolavirus, Sudan ebolavirus and Bundibungyoebolavirus. Although Zaireebolavirus (EBOV) is known to be the deadliest species, some EBOV-infected individuals can completely resist this virus whereas others develop lethal disease and succumb to Ebola virus disease (EVD). Thus, the main goal of this doctoral project was to investigate the genetic profiles of innate immune-related genes in EBOV-infected individuals, and to assess their relationship with clinical outcome of the disease. Additionally, we aimed to identify the genetic variants, predominantly single nucleotide polymorphisms (SNPs), involved in EBOV susceptibility or resistance and to assess their influence on EVD outcome.

This doctoral thesis shows that EBOV-infected individuals have diverse Human Leukocyte Antigen (HLA) and Killer cell Immunoglobulin-like Receptor (KIR) genotype profiles, which may influence EVD outcome. The activating KIR 2DS4-003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; and KIR 2DL2 was more common among EVD survivors. Investigating the genetic markers associated with immune-related genes from EBOV-infected individuals may provide new insights into the mechanisms underlying the clinical outcome of EVD and facilitate the development of new therapeutic approaches.