Targeted modification of the foot-and-mouth disease virus genome for quick cell culture adaptation : [Preprint]

Dill, Veronika GND; Zimmer, Aline; Beer, Martin GND; Eschbaumer, Michael GND

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 passagedderived 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.

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Dill, Veronika / Zimmer, Aline / Beer, Martin / et al: Targeted modification of the foot-and-mouth disease virus genome for quick cell culture adaptation. [Preprint]. 2020.

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