Pathogen Genomics Phenotype and Immunity/Zika: Is the Ugandan Population Vulnerable to a Zika Virus Epidemic?

Lead Research Organisation: MRC/UVRI Uganda Research Unit on AIDS

Abstract

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Technical Summary

This pilot study will address the question, whether Uganda is vulnerable to a Zika virus
(ZIKV) epidemic. Since its discovery in 1947, no evidence of endemic/epidemic ZIKV
infection has been found in Uganda. However, a virulent, pathogenic ZIKV lineage has
emerged in Asia, quickly spreading to other continents. The emergence of this lineage raises
the question, whether ZIKV strains from Uganda are non-pathogenic or if Ugandans have
built immunity over time or through cross-reactivity to related viral species.
Our aims are 1) to search for ZIKV among mosquitoes and key human cohorts and 2) to
molecularly and phylogenetically characterize Ugandan strains.
To this end, a large mosquito collection representing a broad geographical distribution with
seasonal variation will be screened for ZIKV RNA by RT-PCR and full ZIKV genomes
molecularly characterized using metagenomics next generation sequencing on the MiSeq
platform.
ZIKV sequences derived from mosquitoes will be phylogenetically compared to estimate
evolutionary radiation and divergence from the 1947 strain.
Similarly, stored samples from key human populations (Measles/Rubella Surveillance and
Acute Febrile Illness cohorts, and AIDS Indicator Surveys) will be screened for ZIKV RNA.
Plasma ZIKV sequences will be phylogenetically compared to local mosquitoes sequences and
African/Asian lineages (GenBank). Clinical specimens will also be screened serologically for
evidence of past exposure to ZIKV, already in use at UVRI.
The data generated through this study will form the foundation for further studies to evaluate
Ugandan ZIKV as a prototype target for the development of ZIKV-specific diagnostic assays
and the development of a vaccine using a non-pathogenic live/attenuated strain of the virus.

Publications

10 25 50
 
Description MRC-Zika virus funding
Amount £150,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2016 
End 03/2018
 
Title Next Generation Sequencing-including metagenomics (not discovered by our group, but commercially available) 
Description The tool introduced is being used for next genration equencing to idetify new viruses and to sequence HIV 
Type Of Material Improvements to research infrastructure 
Year Produced 2016 
Provided To Others? Yes  
Impact Quicker generation of results and discovery of viruses 
 
Title Rare and New viruses identified 
Description In the process of looking for Zika virus, we have identified rare viruses and a new virus. This has been done in collaboration. The biological materials generated can be used to develop diagnostic tools for these viruses and to understand more the diseases associated with these viruses 
Type Of Material Biological samples 
Year Produced 2017 
Provided To Others? No  
Impact These materials will be used to develop diagnostic tools 
 
Description Metagenomics analyses with Glasgow University 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided specimens. We have received sequences generated at Glasgow for analysis at UVRI. We have participated in writing of new research grants. We have worked with the team to present data to the research community and to the local communities in West Nile where a new virus was isolated
Collaborator Contribution They have trained our staff in metagenomics, and contributed to the transfer of technology. Three of our staff have visited Glasgow and a team led by Dr Emma Thompson has also visited us. We are together writing other research grants
Impact In the process of looking for Zika virus, we have also identified other viruses including Le Dantec Rhabdovirus. Metagenomic analysis of the acute plasma RNA revealed a contiguous sequence of 11,423 nucleotides that had a 94% identity with a 1965 LDV strain isolated from a Senegalese girl (DakHD763 strain, KM205006) by phylogenetic analysis. The metagenomics sequence was confirmed by PCR and Sanger sequencing of a 5'-half genome fragment. We have also identified a new virus named Adumi virus, from a girl in West Nile region
Start Year 2015
 
Description Partnership with UVRI on Zika virus studies 
Organisation Uganda Virus Research Institute
Department Department of Arbovirology, Emerging and Re-emerging Infections
Country Uganda 
Sector Public 
PI Contribution We provide sequencing expertise and its analyses. We have provided facilities to analyse more samples. We have provided training opportunities to UVRI staff including those studying for MSc and PhD
Collaborator Contribution UVRI provides mosquito and human specimens to analyse. They also perform some other analyses such as the plaque neutralization reduction assays, and characterization of the mosquitoes from which we are looking for viruses.
Impact We have analysed a number of samples, this has led to more collaboration with other partners such as USA CDC and University of Glasgow. In the process of this work we have identified Le Dantec virus, only previously identified in two people in West Africa and in UK
Start Year 2015
 
Description A presentation on Zika activities at the UNESCO-Merck Africa Researchers Summit in Ethiopia, November 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact This was the 2nd edition of the UNESCO-Merck Africa Research Summit which attracted a large number of African researchers and of policy makers. Over 150 researchers participated. The focus/theme was 'Infectious Diseases and Women's Health'. There were for abstracts (for posters) from young African scientists who attended the Summit.
Year(s) Of Engagement Activity 2016
 
Description Media interview on Zika in Uganda 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I was interviewed by both local and international media on the status of Zika in Uganda. Providing information as to whether Zika virus is circulating in Uganda. There was concern and this had also affected travel, with some visitors worried about contracting Zika in Uganda.
Year(s) Of Engagement Activity 2016,2017