In vitro surrogate models to aid in the development of antivirals for the containment of foot-and-mouth disease outbreaks

Osiceanu, Ana Maria; Murao, Lyre Espada; Kollanur, Denny; Swinnen, John; Vleeschauwer, Annebel R. De; Lefebvre, David; Clercq, Kris De; Neyts, Johan; Goris, Nesya

doi:10.1016/j.antiviral.2014.02.009

Cited by 9 publications

(7 citation statements)

References 27 publications

(21 reference statements)

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“…For FMDV, the picornavirus Senecavirus A (SVA) was used, while Bovine Viral Diarrhea Virus (BVDV), Bovine Herpesvirus Type 1 (BHV-1), Canine Distemper Virus (CDV), Porcine Sapelovirus (PSV) and Feline Calicivirus, were used as surrogates for CSFV, PRV, NiV, SVDV and VESV, respectively. Surrogate viruses are commonly used to study different aspects of foreign animal disease agents, including studies addressing the environmental stability and the efficacy of disinfectants against these viruses [ 16 – 23 ]. To ensure that surrogate viruses accurately represented target viruses, selection criteria required that both the target and the surrogate were classified in the same viral family, with the closest available virus within the subfamily and/or genus being selected [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Survival of viral pathogens in animal feed ingredients under transboundary shipping models

et al. 2018

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The goal of this study was to evaluate survival of important viral pathogens of livestock in animal feed ingredients imported daily into the United States under simulated transboundary conditions. Eleven viruses were selected based on global significance and impact to the livestock industry, including Foot and Mouth Disease Virus (FMDV), Classical Swine Fever Virus (CSFV), African Swine Fever Virus (ASFV), Influenza A Virus of Swine (IAV-S), Pseudorabies virus (PRV), Nipah Virus (NiV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Swine Vesicular Disease Virus (SVDV), Vesicular Stomatitis Virus (VSV), Porcine Circovirus Type 2 (PCV2) and Vesicular Exanthema of Swine Virus (VESV). Surrogate viruses with similar genetic and physical properties were used for 6 viruses. Surrogates belonged to the same virus families as target pathogens, and included Senecavirus A (SVA) for FMDV, Bovine Viral Diarrhea Virus (BVDV) for CSFV, Bovine Herpesvirus Type 1 (BHV-1) for PRV, Canine Distemper Virus (CDV) for NiV, Porcine Sapelovirus (PSV) for SVDV and Feline Calicivirus (FCV) for VESV. For the remaining target viruses, actual pathogens were used. Virus survival was evaluated using Trans-Pacific or Trans-Atlantic transboundary models involving representative feed ingredients, transport times and environmental conditions, with samples tested by PCR, VI and/or swine bioassay. SVA (representing FMDV), FCV (representing VESV), BHV-1 (representing PRV), PRRSV, PSV (representing SVDV), ASFV and PCV2 maintained infectivity during transport, while BVDV (representing CSFV), VSV, CDV (representing NiV) and IAV-S did not. Notably, more viruses survived in conventional soybean meal, lysine hydrochloride, choline chloride, vitamin D and pork sausage casings. These results support published data on transboundary risk of PEDV in feed, demonstrate survival of certain viruses in specific feed ingredients (“high-risk combinations”) under conditions simulating transport between continents and provide further evidence that contaminated feed ingredients may represent a risk for transport of pathogens at domestic and global levels.

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Section: Methodsmentioning

confidence: 99%

Survival of viral pathogens in animal feed ingredients under transboundary shipping models

et al. 2018

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“…[25][26][27] While these strategies have enabled HTS to be performed with these pathogens at facilities that do not have access to BSL-4 laboratories, the concern is that these artificial systems may not accurately reflect all the antiviral targets of the virulent pathogen. 28 BSL-4 work has historically been low throughput, relying on visual observation of cytopathic effect (CPE) and quantitation of virus titer by plaque assay or by qPCR. These manual processes are not scalable to the levels of throughput needed to conduct HTS campaigns.…”

Section: Process Design and Development For Bsl-4 Htsmentioning

confidence: 99%

“…These manual processes are not scalable to the levels of throughput needed to conduct HTS campaigns. 28 Recently, high-content imaging was used with Ebola VLPs to screen compound libraries at BSL-2 29 and for several BSL-4 pathogens, 30 but the actual imaging of the samples was conducted at the BSL-2. This required extensive fixation of samples to inactivate the virus before removal from containment.…”

Section: Process Design and Development For Bsl-4 Htsmentioning

confidence: 99%

Adapting High-Throughput Screening Methods and Assays for Biocontainment Laboratories

Rasmussen

Tigabu

White

et al. 2015

ASSAY and Drug Development Technologies

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High-throughput screening (HTS) has been integrated into the drug discovery process, and multiple assay formats have been widely used in many different disease areas but with limited focus on infectious agents. In recent years, there has been an increase in the number of HTS campaigns using infectious wild-type pathogens rather than surrogates or biochemical pathogen-derived targets. Concurrently, enhanced emerging pathogen surveillance and increased human mobility have resulted in an increase in the emergence and dissemination of infectious human pathogens with serious public health, economic, and social implications at global levels. Adapting the HTS drug discovery process to biocontainment laboratories to develop new drugs for these previously uncharacterized and highly pathogenic agents is now feasible, but HTS at higher biosafety levels (BSL) presents a number of unique challenges. HTS has been conducted with multiple bacterial and viral pathogens at both BSL-2 and BSL-3, and pilot screens have recently been extended to BSL-4 environments for both Nipah and Ebola viruses. These recent successful efforts demonstrate that HTS can be safely conducted at the highest levels of biological containment. This review outlines the specific issues that must be considered in the execution of an HTS drug discovery program for high-containment pathogens. We present an overview of the requirements for HTS in high-level biocontainment laboratories.

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“…Since FMDV is an extremely contagious and pathogenic aphthovirus that can only be manipulated in high-containment biosafety level 3 facilities, the utilization of ERAV as a surrogate for FMDV research has increased in recent years. In this way, ERAV is gaining interest as a suitable model to study aphthovirus cell entry and uncoating or antiviral testing (4)(5)(6). Apart from its potential as an alternative tool for FMDV research, the plasticity of its capsid has made of ERAV an interesting model virus for analyzing the structural rearrangements of picornavirus capsids (4,7).…”

Section: Importancementioning

confidence: 99%

Equine Rhinitis A Virus Mutants with Altered Acid Resistance Unveil a Key Role of VP3 and Intrasubunit Interactions in the Control of the pH Stability of the Aphthovirus Capsid

Caridi

Cañas‐Arranz

Vázquez-Calvo

et al. 2016

J Virol

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Equine rhinitis A virus (ERAV) is a picornavirus associated with respiratory disease in horses and is genetically closely related to foot-and-mouth disease virus (FMDV), the prototype aphthovirus. ERAV has recently gained interest as an FMDV alternative for the study of aphthovirus biology, including cell entry and uncoating or antiviral testing. As described for FMDV, current data support that acidic pH inside cellular endosomes triggers ERAV uncoating. In order to provide further insights into aphthovirus uncoating mechanism, we have isolated a panel of ERAV mutants with altered acid sensitivity and that differed on their degree of sensitivity to the inhibition of endosome acidification. These results provide functional evidence of the involvement of acidic pH on ERAV uncoating within endosomes. Remarkably, all amino acid substitutions found in acid-labile or acid-resistant ERAVs were located in the capsid protein VP3, indicating that this protein plays a pivotal role for the control of pH stability of the ERAV capsid. Moreover, all amino acid substitutions mapped at the intraprotomer interface between VP3 and VP2 or between VP3 and the N terminus of VP1. These results expand our knowledge on the regions that regulate the acid stability of aphthovirus capsid and should be taken into account when using ERAV as a surrogate of FMDV. IMPORTANCEThe viral capsid constitutes a sort of dynamic nanomachine that protects the viral genome against environmental assaults while accomplishing important functions such as receptor attachment for viral entry or genome release. We have explored the molecular determinants of aphthovirus capsid stability by isolating and characterizing a panel of equine rhinitis A virus mutants that differed on their acid sensitivity. All the mutations were located within a specific region of the capsid, the intraprotomer interface among capsid proteins, thus providing new insights into the regions that control the acid stability of aphthovirus capsid. These findings could positively contribute to the development of antiviral approaches targeting aphthovirus uncoating or the refinement of vaccine strategies based on capsid stabilization. E quine rhinitis A virus (ERAV) is a picornavirus associated with febrile respiratory disease in horses (1, 2). Due to its physical properties and its identification as a respiratory pathogen, ERAV was historically classified into the genus Rhinovirus (former Equine rhinovirus-1) of the family Picornaviridae (1). However, because of its resemblance at the nucleotide sequence level and at the genomic structure to foot-and-mouth disease virus (FMDV), ERAV has been reclassified into the Aphthovirus genus (3). Consistently, ERAV is now considered the phylogenetically most closely related virus to FMDV, which actually constitutes the prototype aphthovirus (http://www.ictvonline.org/virusTaxonomy .asp). Since FMDV is an extremely contagious and pathogenic aphthovirus that can only be manipulated in high-containment biosafety level 3 facilities, the utilization o...

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In vitro surrogate models to aid in the development of antivirals for the containment of foot-and-mouth disease outbreaks

Cited by 9 publications

References 27 publications

Survival of viral pathogens in animal feed ingredients under transboundary shipping models

Survival of viral pathogens in animal feed ingredients under transboundary shipping models

Adapting High-Throughput Screening Methods and Assays for Biocontainment Laboratories

Equine Rhinitis A Virus Mutants with Altered Acid Resistance Unveil a Key Role of VP3 and Intrasubunit Interactions in the Control of the pH Stability of the Aphthovirus Capsid

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