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Published on: July 6, 2013
Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals
Haiyan Wei1,2, Jonathan Audet3, Gary Wong2,4
1Institute of Infectious Disease, Henan Center for Disease Control, Henan, China.
Abstract:
Marburg virus (MARV) has caused outbreaks of filoviral hemorrhagic fever since its discovery in 1967. The largest and deadliest outbreak occurred in Angola in 2005, with 252 cases and 227 deaths. In 2014, we developed a mouse-adapted MARV, Angola variant through serial passaging in mice. The mouse-adapted MARV exhibits many of the hallmarks of MARV disease in humans. By applying deep-sequencing to every passage of the virus, we are able to study virus evolution in this host with surprising precision. We show that two regions go through substantial changes: the intergenic region between NP and VP35, as well as the first 100 amino acids of the VP40 protein. Our results also reveal that there were profound changes during the production of the final virus stock in cell culture. Overall, our results show that a handful of regions carry most of the mutations acquired during the adaptation of the virus to a new host and that many mutations become fixed very early during the adaptation process.
Insights
Researchers adapted Marburg virus (MARV) to mice, revealing key genetic changes in specific regions. This adaptation process shows mutations occur early and are concentrated in limited areas during host transition.
Area of Science:
- Virology
- Molecular Biology
- Pathogen Adaptation
Background:
- Marburg virus (MARV) causes severe hemorrhagic fever, with a notable outbreak in Angola in 2005.
- Understanding MARV evolution is crucial for developing effective countermeasures.
Purpose of the Study:
- To investigate the evolutionary changes of Marburg virus during adaptation to a new host (mice).
- To identify specific viral genomic regions that undergo significant alterations during mouse adaptation.
Main Methods:
- Development of a mouse-adapted MARV Angola variant through serial passaging in mice.
- Application of deep-sequencing to analyze viral genomes at each passage stage.
- Analysis of genetic changes in intergenic regions and viral proteins.
Main Results:
- Significant genetic alterations were observed in the intergenic region between NP and VP35, and the N-terminal 100 amino acids of VP40.
- Profound genetic changes were also noted during the production of the final virus stock in cell culture.
- A limited number of genomic regions accumulated the majority of mutations during host adaptation, with early fixation of many mutations.
Conclusions:
- The adaptation of Marburg virus to mice involves substantial genetic changes concentrated in specific genomic regions.
- Early and rapid fixation of mutations is a key characteristic of MARV adaptation to a new host.
- The study provides precise insights into viral evolution during host jumps, relevant for understanding filovirus emergence.
