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Within-Host Recombination in the Foot-and-Mouth Disease Virus Genome
Luca Ferretti1, Antonello Di Nardo2, Benjamin Singer3
1The Pirbright Institute, Ash Road, Woking, Surrey GU24 0NF, UK. luca.ferretti@pirbright.ac.uk.
Abstract:
Recombination is one of the determinants of genetic diversity in the foot-and-mouth disease virus (FMDV). FMDV sequences have a mosaic structure caused by extensive intra- and inter-serotype recombination, with the exception of the capsid-encoding region. While these genome-wide patterns of broad-scale recombination are well studied, not much is known about the patterns of recombination that may exist within infected hosts. In addition, detection of recombination among viruses evolving at the within-host level is challenging due to the similarity of the sequences and the limitations in differentiating recombination from point mutations. Here, we present the first analysis of recombination events between closely related FMDV sequences occurring within buffalo hosts. The detection of these events was made possible by the occurrence of co-infection of two viral swarms with about 1% nucleotide divergence. We found more than 15 recombination events, unequally distributed across eight samples from different animals. The distribution of these events along the FMDV genome was neither uniform nor related to the phylogenetic distribution of recombination breakpoints, suggesting a mismatch between within-host evolutionary pressures and long-term selection for infectivity and transmissibility.
Insights
Foot-and-mouth disease virus (FMDV) recombination within hosts is challenging to detect. This study reveals over 15 recombination events in buffalo, showing non-uniform distribution across the FMDV genome.
Area of Science:
- Virology
- Molecular Evolution
- Genetics
Background:
- Recombination is a key driver of genetic diversity in foot-and-mouth disease virus (FMDV).
- While genome-wide recombination patterns are known, within-host FMDV recombination remains poorly understood.
- Detecting within-host recombination is difficult due to sequence similarity and challenges in distinguishing it from point mutations.
Purpose of the Study:
- To investigate recombination events between closely related FMDV sequences within buffalo hosts.
- To analyze the patterns and distribution of within-host FMDV recombination across the viral genome.
Main Methods:
- Analysis of FMDV sequences from co-infected buffalo, exhibiting approximately 1% nucleotide divergence.
- Identification and characterization of recombination events within infected host samples.
- Assessment of recombination event distribution across the FMDV genome and comparison with phylogenetic data.
Main Results:
- Over 15 recombination events were detected across eight buffalo samples.
- Recombination events were unequally distributed among the samples.
- The genomic distribution of within-host recombination was non-uniform and did not correlate with known long-term recombination breakpoint patterns.
Conclusions:
- This study provides the first evidence of recombination between closely related FMDV strains within a host.
- Within-host recombination patterns differ from those observed at broader evolutionary scales.
- A potential mismatch exists between within-host evolutionary pressures and the long-term selection pressures driving FMDV infectivity and transmissibility.
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