Dataset Information

Genetic Determinants of Virulence between Two Foot-and-Mouth Disease Virus Isolates Which Caused Outbreaks of Differing Severity.

ABSTRACT: Individual foot-and-mouth disease virus (FMDV) strains reveal different degrees of infectivity and pathogenicity in host animals. The differences in severity among outbreaks might be ascribable to these differences in infectivity among FMDV strains. To investigate the molecular mechanisms underlying these differences, we estimated the infectivity of O/JPN/2000 and O/JPN/2010, which caused outbreaks of markedly different scales, in cell lines, Holstein cattle, and suckling mice. Viral growth of the two strains in cells was not remarkably different; however, O/JPN/2000 showed apparently low transmissibility in cattle. Mortality rates of suckling mice inoculated intraperitoneally with a 50% tissue culture infective dose (TCID50) of 10 for O/JPN/2000 and O/JPN/2010 also differed, at 0% and 100%, respectively. To identify genes responsible for this difference in infectivity, genetic regions of the full-length cDNA of O/JPN/2010 were replaced with corresponding fragments of O/JPN/2000. A total of eight recombinant viruses were successfully recovered, and suckling mice were intraperitoneally inoculated. Strikingly, recombinants having either VP1 or 3D derived from O/JPN/2000 showed 0% mortality in suckling mice, whereas other recombinants showed 100% mortality. This finding indicates that VP1, the outermost component of the virus particle, and 3D, an RNA-dependent RNA polymerase, are individually involved in the virulence of O/JPN/2010. Three-dimensional structural analysis of VP1 confirmed that amino acid differences between the two strains were located mainly at the domain interacting with the cellular receptor. On the other hand, measurement of their mutation frequencies demonstrated that O/JPN/2000 had higher replication fidelity than O/JPN/2010.IMPORTANCE Efforts to understand the universal mechanism of foot-and-mouth disease virus (FMDV) infection may be aided by knowledge of the molecular mechanisms which underlie differences in virulence beyond multiple topotypes and serotypes of FMDV. Here, we demonstrated independent genetic determinants of two FMDV isolates which have different transmissibility in cattle, namely, VP1 and 3D protein. Findings suggested that the selectivity of VP1 for host cell receptors and replication fidelity during replication were important individual factors in the induction of differences in virulence in the host as well as in the severity of outbreaks in the field. These findings will aid the development of safe live vaccines and antivirals which obstruct viral infection in natural hosts.

SUBMITTER: Nishi T

PROVIDER: S-EPMC6695517 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic Determinants of Virulence between Two Foot-and-Mouth Disease Virus Isolates Which Caused Outbreaks of Differing Severity.

Nishi Tatsuya T Morioka Kazuki K Saito Nobuko N Yamakawa Makoto M Kanno Toru T Fukai Katsuhiko K

mSphere 20190814 4

Individual foot-and-mouth disease virus (FMDV) strains reveal different degrees of infectivity and pathogenicity in host animals. The differences in severity among outbreaks might be ascribable to these differences in infectivity among FMDV strains. To investigate the molecular mechanisms underlying these differences, we estimated the infectivity of O/JPN/2000 and O/JPN/2010, which caused outbreaks of markedly different scales, in cell lines, Holstein cattle, and suckling mice. Viral growth of t ...[more]

PMID: 31413173

Similar Datasets

Project description:Under different circumstances, the alteration of several viral genes may give an evolutionary advantage to the virus to maintain its prevalence in nature. In this study, a 70-nucleotide deletion in the small fragment (S fragment) of the viral 5'-untranslated region (5'-UTR) together with one amino acid insertion in the leader protein (Lpro) that naturally occurred in several serotype O foot-and-mouth disease virus (FMDV) strains in China was identified. The properties of two field serotype O FMDV strains, with or without the 70-nucleotide deletion in the S fragment and the amino acid insertion in Lpro, were compared in vitro and in vivo Clinical manifestations of FMD were clearly observed in cattle and pigs infected by the virus without the mutations. However, the virus with the mentioned mutations caused FMD outcomes only in pigs, not in cattle. To determine the role of the 70-nucleotide deletion in the S fragment and the single amino acid insertion in Lpro in the pathogenicity and host range of FMDV, four recombinant viruses, with complete genomes and a 70-nucleotide deletion in the S fragment, a single amino acid insertion in Lpro, or both mutations, were constructed and rescued. It showed that deletion of 70 nucleotides in the S fragment or insertion of one amino acid (leucine) at position 10 of Lpro partly decreased the viral pathogenicity of Mya-98 lineage virus in cattle and pigs. However, the virus with dual mutations caused clinical disease only in pigs, not in cattle. This suggested that the S fragment and Lpro are significantly associated with the virulence and host specificity of FMDV. The naturally occurring dual mutation in the S fragment and Lpro is a novel determinant of viral pathogenicity and host range for serotype O FMDV.IMPORTANCE FMD is probably the most important livestock disease in the world due to the severe economic consequences caused. The alteration of several viral genes may give the virus selective advantage to maintain its prevalence in nature. Here, we identified that a 70-nucleotide deletion in the S fragment combined with a single leucine insertion in the leader protein (Lpro) is a novel determinant of restricted growth on bovine cells, which significantly contributes to the altered virulence of serotype O FMDV in cattle. A synergistic and additive effect of the 70-nucleotide deletion in the S fragment and the single leucine insertion in Lpro on the virulence and host specificity of the virus was determined. These results will benefit efforts to understand the vial pathogenicity mechanism and molecular characteristics of FMDV.

Dataset Information

Genetic Determinants of Virulence between Two Foot-and-Mouth Disease Virus Isolates Which Caused Outbreaks of Differing Severity.

Publications

Genetic Determinants of Virulence between Two Foot-and-Mouth Disease Virus Isolates Which Caused Outbreaks of Differing Severity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets