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

• Published in: PloS one Vol. 13; no. 2; p. e0190977
• Main Authors: Ramirez-Carvajal, Lisbeth, Pauszek, Steven J, Ahmed, Zaheer, Farooq, Umer, Naeem, Khalid, Shabman, Reed S, Stockwell, Timothy B, Rodriguez, Luis L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2018; Public Library of Science (PLoS)
• Subjects: 60 APPLIED LIFE SCIENCES; Amino acids; Analysis; Animal diseases; Animals; Antigens; Biological evolution; Biology and Life Sciences; Bovidae; Codons; Computer and Information Sciences; Disease control; Divergence; Dynamic tests; Epidemics; Epidemiology; Foot & mouth disease; Foot and mouth disease; Foot and mouth disease virus; Gene expression; Gene sequencing; Genetic aspects; Genomes; Genomics; Health aspects; Host-virus relationships; Infections; Livestock; Nucleotides; Pathogenesis; Persistent infection; Phylogenetic analysis; Phylogenetics; Phylogeny; Positive selection; Progeny; Proteins; Research and Analysis Methods; Science & technology - other topics; Structural proteins; Vaccination; Venter, J Craig; Viral evolution; Viral genetics; Viral genomics; Viral persistence and latency; Viruses; VP1 protein; Water buffalo; Wildlife; New York; Pakistan; Islamabad Pakistan; United States > US; Asia; Tennessee; Plum Island; Maryland; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0190977

Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions 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 with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.