scholarly journals The evolution of a super-swarm of foot-and-mouth disease virus in cattle

2019 ◽  
Author(s):  
Jonathan Arzt ◽  
Ian Fish ◽  
Steven J. Pauszek ◽  
Shannon L. Johnson ◽  
Patrick S. Chain ◽  
...  

AbstractFoot-and-mouth disease (FMD) is a highly contagious viral disease that severely impacts global food security and is one of the greatest constraints on international trade of animal products. Extensive viral population diversity and rapid, continuous mutation of circulating FMD viruses (FMDVs) pose significant obstacles to the control and ultimate eradication of this important transboundary pathogen. The current study investigated mechanisms contributing to within-host evolution of FMDV in a natural host species (cattle). Specifically, vaccinated and non-vaccinated cattle were infected with FMDV under controlled, experimental conditions and subsequently sampled for up to 35 days to monitor viral genomic changes as related to phases of disease and experimental cohorts. Consensus-level genomic changes across the entire FMDV coding region were characterized through three previously defined stages of infection: early, transitional, and persistent. The overall conclusion was that viral evolution occurred via a combination of two mechanisms: emergence of full-genomic minority haplotypes from within the inoculum super-swarm, and concurrent continuous point mutations. Phylogenetic analysis indicated that individuals were infected with multiple distinct haplogroups that were pre-existent within the ancestral inoculum used to infect all animals. Multiple shifts of dominant viral haplotype took place during the early and transitional phases of infection, whereas few shifts occurred during persistent infection. These insights into FMDV population dynamics have important implications for virus sampling methodology and molecular epidemiology.

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Aiguo Xin ◽  
Mingwang Zhu ◽  
Zhenqi Peng ◽  
Qi Hu ◽  
Chenhong Shi ◽  
...  

The molecular basis of attenuation of foot-and-mouth disease virus (FMDV) serotype Asia1 ZB strain remains unknown. To understand the genetic changes of attenuation, we compared the entire genomes of three different rabbit-passaged attenuated ZB strains (ZB/CHA/58(att), ZBRF168, and ZBRF188) and their virulent parental strains (ZBCF22 and YNBS/58). The results showed that attenuation may be brought about by 28 common amino acid substitutions in the coding region, with one nucleotide point mutation in the 5′-untranslated region (5′-UTR) and another one in the 3′-UTR. In addition, a total of 21 nucleotides silent mutations had been found after attenuation. These substitutions, alone or in combination, may be responsible for the attenuated phenotype of the ZB strain in cattle. This will contribute to elucidation of attenuating molecular basis of the FMDV ZB strain.


2005 ◽  
Vol 79 (12) ◽  
pp. 7698-7706 ◽  
Author(s):  
Arabinda Nayak ◽  
Ian G. Goodfellow ◽  
Graham J. Belsham

ABSTRACT The 5′ terminus of picornavirus genomic RNA is covalently linked to the virus-encoded peptide 3B (VPg). Foot-and-mouth disease virus (FMDV) is unique in encoding and using 3 distinct forms of this peptide. These peptides each act as primers for RNA synthesis by the virus-encoded RNA polymerase 3Dpol. To act as the primer for positive-strand RNA synthesis, the 3B peptides have to be uridylylated to form VPgpU(pU). For certain picornaviruses, it has been shown that this reaction is achieved by the 3Dpol in the presence of the 3CD precursor plus an internal RNA sequence termed a cis-acting replication element (cre). The FMDV cre has been identified previously to be within the 5′ untranslated region, whereas all other picornavirus cre structures are within the viral coding region. The requirements for the in vitro uridylylation of each of the FMDV 3B peptides has now been determined, and the role of the FMDV cre (also known as the 3B-uridylylation site, or bus) in this reaction has been analyzed. The poly(A) tail does not act as a significant template for FMDV 3B uridylylation.


2013 ◽  
Vol 189 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Lizhe Xu ◽  
William Hurtle ◽  
Jessica M. Rowland ◽  
Karissa A. Casteran ◽  
Stacey M. Bucko ◽  
...  

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 129 ◽  
Author(s):  
Michael Eschbaumer ◽  
Veronika Dill ◽  
Jolene C. Carlson ◽  
Jonathan Arzt ◽  
Carolina Stenfeldt ◽  
...  

Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant viruses lacking the leader protease coding region have been proposed as a safer alternative for the production of inactivated FMD vaccines (Uddowla et al., 2012, J Virol 86:11675-85). In addition to the leader deletion, the marker vaccine virus FMDV LL3BPVKV3DYR A24 encodes amino acid substitutions in the viral proteins 3B and 3D that allow the differentiation of infected from vaccinated animals and has been previously shown to be effective in cattle and pigs. In the present study, two groups of six pigs each were inoculated with live FMDV LL3BPVKV3DYR A24 virus either intradermally into the heel bulb (IDHB) or by intra-oropharyngeal (IOP) deposition. The animals were observed for 3 or 5 days after inoculation, respectively. Serum, oral and nasal swabs were collected daily and a thorough postmortem examination with tissue collection was performed at the end of the experiment. None of the animals had any signs of disease or virus shedding. Virus was reisolated from only one serum sample (IDHB group, sample taken on day 1) and one piece of heel bulb skin from the inoculation site of another animal (IDHB group, necropsy on day 3), confirming that FMDV LL3BPVKV3DYR A24 is highly attenuated in pigs.


2002 ◽  
Vol 128 (2) ◽  
pp. 301-312 ◽  
Author(s):  
S. ALEXANDERSEN ◽  
I. BROTHERHOOD ◽  
A. I. DONALDSON

Foot-and-mouth disease virus (FMDV) can spread by a variety of mechanisms, including, under certain circumstances, by the wind. Simulation models have been developed to predict the risk of airborne spread of FMDV and have played an important part in decision making during emergencies. The minimal infectious dose of FMDV for different species by inhalation is an important determinant of airborne spread. Whereas the doses for cattle and sheep have been quantified, those for pigs are not known. The objective of the study was to obtain that data in order to enhance the capability of simulation models. Under experimental conditions, forty pigs were exposed individually to naturally generated aerosols of FMDV, strain O1 Lausanne. The results indicated that doses under 100 TCID50 failed to infect pigs but doses of approximately 300 TCID50 caused short-term sub-clinical infection. The calculations suggested that a dose of more than 800 TCID50 is required to cause infection and typical disease.


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