Analysis and inhibition of chikungunya virus replication
Lead Research Organisation:
University of Leeds
Department Name: Astbury Centre
Abstract
Background:
Chikungunya virus (CHIKV) is a positive single-stranded RNA virus transmitted by mosquitos. It re-emerged as an epidemic in 2005 around the Indian Ocean, before spreading across Asia, Africa, Europe and North/South America. CHIKV can establish persistent infection causing chronic debilitating musculoskeletal pain and neurological complications. There is no vaccine or antiviral therapy, with development hampered by lack of insight into CHIKV biology. Consequently, there is pressing need to understand how the virus controls replication and identify antiviral targets.
Objectives and experimental approach:
1. Define stem-loop functional domains by mutagenesis and analysis of replication in infectious virus and sub-genomic replicon systems.
2. Disect cellular trans-activating partners by affinity tagged RNA stem-loops, mass spectroscopy and CRISPR inhibition. In particular we will examine factors with similar roles in related viruses (such as PABP/PCBP).
3. Replication inhibition using RNA aptamers and non-antibody binding proteins (adhirons) selected against stem-loop domains.
Novelty: CHIKV replication is poorly understood and the functional RNA structures analysed in this study are novel (manuscript in preparation).
Timeliness:
With no vaccine or antiviral therapy CHIKV is major public health issue and economic burden. It has reached epidemic levels in various areas and continues to spread into regions harbouring its mosquito vector (Ae. albopictus), including much of the USA and Western Europe.
Chikungunya virus (CHIKV) is a positive single-stranded RNA virus transmitted by mosquitos. It re-emerged as an epidemic in 2005 around the Indian Ocean, before spreading across Asia, Africa, Europe and North/South America. CHIKV can establish persistent infection causing chronic debilitating musculoskeletal pain and neurological complications. There is no vaccine or antiviral therapy, with development hampered by lack of insight into CHIKV biology. Consequently, there is pressing need to understand how the virus controls replication and identify antiviral targets.
Objectives and experimental approach:
1. Define stem-loop functional domains by mutagenesis and analysis of replication in infectious virus and sub-genomic replicon systems.
2. Disect cellular trans-activating partners by affinity tagged RNA stem-loops, mass spectroscopy and CRISPR inhibition. In particular we will examine factors with similar roles in related viruses (such as PABP/PCBP).
3. Replication inhibition using RNA aptamers and non-antibody binding proteins (adhirons) selected against stem-loop domains.
Novelty: CHIKV replication is poorly understood and the functional RNA structures analysed in this study are novel (manuscript in preparation).
Timeliness:
With no vaccine or antiviral therapy CHIKV is major public health issue and economic burden. It has reached epidemic levels in various areas and continues to spread into regions harbouring its mosquito vector (Ae. albopictus), including much of the USA and Western Europe.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011151/1 | 01/10/2015 | 30/09/2023 | |||
| 1774743 | Studentship | BB/M011151/1 | 01/10/2016 | 31/03/2021 |