INFLUENZA; Exciting times as first whole-genome dataset from Uganda is generated

Grace Nabakooza has so far generated over 200 influenza MiSeq whole genomes from surveillance samples collected across Uganda by teams at the Uganda Virus Research Institute (UVRI) between 2010 and 2018. This is the first influenza whole-genome dataset from Uganda. In April 2018 Grace was awarded a Wellcome Trust Uganda PhD Fellowship in Infection and Immunity through MUII-Plus. Under this fellowship, she is using phylogenetic analysis and mathematical modelling to study influenza transmission in Africa.

With her PhD research, Grace has set out to generate her own Ugandan influenza whole genomes and study how the viruses have emerged, evolved and diverged for the last 9 years. She has also merged the data with viruses from Africa and the rest of the world to determine how and where the viruses introduced in Uganda originated from. She hopes to answer these using current bioinformatics and molecular phylogenetic methods. Grace chose the area of influenza because she thought not a lot had been done in the area of influenza in Uganda and particularly Africa. ‘I wanted to fill up the gap on this contagious disease, plus I wanted to contribute to the vaccine developments, she said.

Influenza (also called flu) is a highly contagious respiratory infection caused by the influenza virus. Influenza virus(es) has existed in the world for over two centuries but was only first isolated from humans in 1933. The virus has 2 main antigenic molecules on its outer most layer that continuously and rapidly evolve over time causing deadly influenza outbreaks and pandemics. The latest human pandemic in Uganda (across Africa) was in 2009 caused by the H1N1 viral strain similar to that which claimed about 50 million lives during the 1918 Spanish flu. Because of the unpredictable behaviour of influenza viruses, scientists are focusing on understanding the viral genetic, antigenic and transmission patterns. Such knowledge is very informative in the development of anti-viral drugs and multi-strain vaccine against influenza which are a great health need especially in sub-Saharan Africa where flu circulates all year round.

The preliminary results show that the pandemic flu viruses were introduced in Uganda way before they were reported in June 2009. Grace has also observed that the Ugandan viruses are undergoing a genetic drift with viruses evolving every year. These changes are characterized by nonsynonymous mutations that might impact on the virulence and drug susceptibility of the virus. ‘I can’t mention Ugandan flu and leave out the ‘survival for the fittest’ phrase. This is because I observed a particular lineage that emerged and then went extinct within just the last 9 years. This lineage is a good candidate for further investigation,’ she noted.

Currently, Grace has integrated the Ugandan viruses together with the global viruses and is working on a pipeline to visualise the global connectivity of influenza. ‘This is pretty exciting because I have a considerable number of African sequences to confidently map on the influenza global network,’ Grace said.

Knowing how the viruses have evolved through time across Uganda and Africa as a whole, will not only be informative but will also be evidence to predict potential pandemic strains. The Ugandan whole genomes dataset will be made available publicly for future projects in the near future. Simply put, Grace’s work is a great foundation for more exciting projects in influenza genome analysis and modelling studies in Uganda and the whole of Africa.

Grace Nabakooza is a MUII-Plus PhD fellow and holds a Bachelor’s Degree in Biochemistry and Mathematics from Makerere University. After her graduate studies, she worked as a laboratory technologist at the Medical Research Council/ Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, on a project that investigated the immune responses of Ugandan infants to Tuberculosis BCG vaccine. While working on this project, Grace mastered the skills of using various immune response quantification and characterization techniques such as Flow Cytometry. The TB project generated massive interesting data, which inspired Grace to obtain more data analysis and management skills by pursuing a career in Bioinformatics. In 2018, she successfully completed her master’s degree in Bioinformatics at the University of Edinburgh under the Wellcome Trust Uganda Bioinformatics Masters Fellowship. As part of her masters’ dissertation, Grace worked with Professor Andrew Leigh Brown’s group at the Institute of Evolutionary Biology – University of Edinburg and developed a python pipeline to evaluate and visualize HIV-1 phylogenetic clustering using whole genomes. Grace’s interests cut across pathogen evolution, phylogenetics, epidemiology and mathematical modelling of infectious diseases.