Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Targeted Modification of the Foot-And-Mouth Disease Virus Genome for Quick Cell Culture Adaptation

Version 1 : Received: 29 August 2020 / Approved: 31 August 2020 / Online: 31 August 2020 (06:16:50 CEST)

How to cite: Dill, V.; Zimmer, A.; Beer, M.; Eschbaumer, M. Targeted Modification of the Foot-And-Mouth Disease Virus Genome for Quick Cell Culture Adaptation. Preprints 2020, 2020080712 (doi: 10.20944/preprints202008.0712.v1). Dill, V.; Zimmer, A.; Beer, M.; Eschbaumer, M. Targeted Modification of the Foot-And-Mouth Disease Virus Genome for Quick Cell Culture Adaptation. Preprints 2020, 2020080712 (doi: 10.20944/preprints202008.0712.v1).

Abstract

Foot-and-mouth disease virus (FMDV) causes the highly contagious foot-and-mouth disease, which is characterized by the appearance of vesicles in and around the mouth and feet of cloven-hoofed animals. BHK21 cells are the cell line of choice for the propagation of FMDV for vaccine production world-wide but vary in their susceptibility for different FMDV strains. Previous studies showed that the FMDV resistance of a certain BHK cell line can be overcome by using a closely related but permissive cell line for the pre-adaptation of the virus, but the adapted strains were found to harbor several capsid mutations. In this study, these adaptive mutations were introduced into the original Asia-1 Shamir isolate individually or in combination to create a panel of 17 Asia-1 mutants by reverse genetics and examine the effects of the mutations on receptor usage, viral growth, immunogenicity and stability. A single amino acid exchange from glutamic acid to lysine at position 202 in VP1 turned out to be of major importance for productive infection of the suspension cell line BHK-2P. In consequence, two traditionally passage-derived strains and two recombinant viruses with a minimum set of mutations were tested in vivo. While the passaged-derived viruses showed a reduced particle stability, the genetically modified viruses were more stable but did not confer a protective immune response against the original virus isolate.

Subject Areas

Foot-and-mouth disease virus; serotype Asia-1; BHK suspension cells; mutagenesis; particle stability; neutralizing antibody response; recombinant virus; vaccine production

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