Pathogen Genomics Phenotype and Immunity/Zika: Is the Ugandan Population Vulnerable to a Zika Virus Epidemic?
Lead Research Organisation:
Uganda Virus Research Institute
Department Name: UNLISTED
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.
(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.
People |
ORCID iD |
| 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 | Collaborationwith the Ministry of Health on Research on emerging and re-emeging infections |
| Organisation | Ministry of Health, Uganda |
| Country | Uganda |
| Sector | Public |
| PI Contribution | We are conducting surveillance studies for new and re-ermerging viruses. We look for funding, collaborations and conduct some of the studies locally |
| Collaborator Contribution | The Ministry of Health Departments offer the environment to work in different surveillance sites and some epidemiological expertise |
| Impact | Publications, policies, and valuable samples |
| Start Year | 2016 |
| 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 |