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.
Highlights
The foot-and-mouth disease virus (FMDV) is a prototypical member of the genus Aphthovirus, family Picornaviridae, together with bovine rhinitis A virus, bovine rhinitis B virus, and equine rhinitisA virus [1]
The linkage disequilibrium between variants decreases : initially, the LD is at its highest possible value, but it decreases in time as D = Dmax e−r·t, where t is the time since the origin of the multi-swarm and r is the recombination rate for the interval between the Single Nucleotide Polymorphisms (SNPs)
Our work does not attempt to make the case for the presence of extensive intra-host recombination for this virus, since overwhelming direct evidence for within-host recombination within the capsid region of SAT1 FMDV genomes was already presented recently in [22] from a complex dataset obtained from a long-term follow-up study conducted in artificially infected buffaloes
Summary
The foot-and-mouth disease virus (FMDV) is a prototypical member of the genus Aphthovirus, family Picornaviridae, together with bovine rhinitis A virus, bovine rhinitis B virus, and equine rhinitisA virus [1]. The foot-and-mouth disease virus (FMDV) is a prototypical member of the genus Aphthovirus, family Picornaviridae, together with bovine rhinitis A virus, bovine rhinitis B virus, and equine rhinitis. The virus can persist for years in carrier animals. These persistent infections occur often in buffaloes and other species where the infection progresses in a subclinical form. Encapsulated in a non-enveloped virion, the FMDV RNA genome (of ∼8.4 kb in size) is surrounded by an icosahedral capsid formed by four structural proteins (VP4 to VP1), with 10 further non-structural proteins (Lpro, 2A, 2B, 2C, 3A, 3B1, 3B2, 3B3, 3Cpro, and 3Dpol) encoded by ten non-capsid coding regions [3]. Structural proteins possess determinants for infections and immunity, whilst the non-structural proteins are responsible for genome processing
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