Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts

Authors: RAMIREZ-CARVAJAL, L - Oak Ridge Institute For Science And Education (ORISE); Pauszek, Steven; AHMED, Z - Oak Ridge Institute For Science And Education (ORISE); FAROOQ, U - National Agricultural Research Center - Pakistan; NAEEM, K - National Agricultural Research Center - Pakistan; SHABMAN, R - J Craig Venter Institute; STOCKWELL, T - J Craig Venter Institute; Rodriguez, Luis

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/23/2017
Publication Date: N/A
Citation: N/A

Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes a devastating disease in livestock (e.g. pigs, cattle, sheep, goats). The disease is widespread in Asia and Africa but it has not occurred in the US since 1929. The introduction of FMDV would have devastating economic consequences to agriculture and related industries in the US. In Pakistan FMDV causes disease in cattle and in Asian buffalo. In the buffalo infections in the absence of clinical signs is common. In order to better understand the role of infected buffalo in transmission, a collaborative study was established between scientists in ARS and the National Agricultural Research Center in Islamabad, Pakistan. Genetic sequences of FMDV obtained using next-generation DNA sequencing methods, showed little change in the virus during long term infections in buffalo. This data indicated that viruses do not easily escape vaccine coverage. Our findings provide insights into the dynamics of FMDV populations within naturally occurring infections and may benefit FMD control strategies.

Technical Abstract: Foot-and-mouth disease (FMD) is a severe viral disease that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of FMDV pathogenesis and a major impediment for disease control. Carrier animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigates the genetic dynamics of FMDV in naturally occurring persistent infections of naturally infected Asian buffalo. We used next-generation sequencing (NGS) to obtain 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Seven of the animals yielded more than one viral isolate of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Few nucleotide variants and non-synonymous substitutions were detected within quasispecies of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals within Group VII. Signature amino acid substitutions and conserved epitopes are described for isolates from this study relative to other genomes available in public databases including members of Group VII. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent infections did not induce a clear pattern of antigenic selection, despite the presence of immune responses against the virus. Our findings provide insights into the evolutionary dynamics of FMDV populations within naturally occurring persistent infections and may benefit FMD control strategies in endemic regions.