Abstract
For gene duplication to be maintained, particularly in the small genomes of RNA viruses, this should offer some advantages. We have investigated the functions of a small protein termed VPg or 3B, which acts as a primer in the replication of foot‐and‐mouth disease virus (FMDV). Many related picornaviruses encode a single copy but uniquely the FMDV genome includes three (nonidentical) copies of the 3B coding region. Using sub‐genomic replicons incorporating nonfunctional 3Bs and 3B fusion products in competition and complementation assays, we investigated the contributions of individual 3Bs to replication and the structural requirements for functionality. We showed that a free N‐terminus is required for 3B to function as a primer and although a single 3B can support genome replication, additional copies provide a competitive advantage. However, a fourth copy confers no further advantage. Furthermore, we find that a minimum of two 3Bs is necessary for trans replication of FMDV replicons, which is unlike other picornaviruses where a single 3B can be used for both cis and trans replication. Our data are consistent with a model in which 3B copy number expansion within the FMDV genome has allowed evolution of separate cis and trans acting functions, providing selective pressure to maintain multiple copies of 3B.
Highlights
The evolution of small ribonucleic acid (RNA) viruses is largely driven by the error-prone RNA-dependent RNA polymerase (RdRp), which is responsible for replicating the viral genome
While gene duplication is common among DNA viruses,[6] it is rarely reported among RNA viruses, it should be noted that the capsid proteins of picornaviruses probably evolved via this mechanism.[7]
We previously showed that some footand-mouth disease virus (FMDV) replicons with replication-disabling substitutions in the 3Dpol active site could be rescued in trans by co-transfection with a second replicon containing a functional 3Dpol
Summary
The evolution of small RNA viruses is largely driven by the error-prone RNA-dependent RNA polymerase (RdRp), which is responsible for replicating the viral genome. The P3 region encodes 3A, triplicate copies of the replication primer, 3B ( known as VPg, ie, 3B1, 3B2, and 3B3), the viral protease 3Cpro and the RdRp termed 3Dpol.[10]. Most picornaviruses, such as the well-studied poliovirus (PV), encode a single copy of 3B and there is evidence for duplication of 3B in some, FMDV is the only picornavirus that has been demonstrated to have three (nonidentical) copies of the 3B coding region. We examine differences in the functions of the individual copies of 3B, which help to explain why possession of multiple copies is advantageous to the virus, and why these persist in the population
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