Antigenic stability of foot-and-mouth disease virus variants on serial passage in cell culture

Abstract

Two neutralizing monoclonal antibody (MAb)-resistant variants selected from an isolate of foot-and-mouth disease virus (FMDV) type A5 were repeatedly passaged in cell culture and monitored for susceptibility to neutralization by the selecting MAb. A variant isolated with a MAb to a conformational epitope (1-OG2) lost resistance in 20 passages, while a variant isolated with a MAb to a linear epitope (1-HA6) persisted for 30 passages. In both cases, the virus population emerging after passage was antigenicaily and genetically indistinguishable from the original wild-type parental virus (FMDV A5 Spain-86). Coinfection assays with the wild type and each variant, and between the variants, showed rapid conversion to a homogeneous population. Wild-type virus prevailed over the variants and for coinfection between the variants, the linear epitope variant 1-HA6. While both variants arose from a single nucleotide substitution and reversion to wild type occurred for each, it appears that the variant based on the continuous epitope (1-HA6) was more stable. We discuss the implications of these results for the antigenic diversity of FMDV and its relationship to virus evolution.

Method for serial passage of infectious hematopoietic necrosis virus (IHNV) in rainbow trout

“…The absence of changes in the G gene also does not eliminate the possibility of changes in other parts of the viral genome. Our results are consistent with previous studies that passage of the virus through a few generations of cell culture does not typically result in virus evolution (Gonzalez et al 1991, Chen et al 2003, Bellec et al 2014. Additional studies examining whether or not multiple rounds of serial passage through fish results in evolution may be enlightening.…”

Evolution of the capsid protein genes of foot-and-mouth disease virus: antigenic variation without accumulation of amino acid substitutions over six decades

“…Foot-and-mouth disease virus (FMDV) is an aphthovirus of the family Picornaviridae which causes an economically important disease of cattle and other cloven-hoofed animals (reviews in references 2, 6, 20, and 57). FMDV populations are genetically and antigenically heterogeneous (9, 12-17, 27, 47, 51, 58, 60, 63), and variants showing different competitive abilities relative to their parental populations arise at high rates (28,46). Thus, the virus conforms to a quasispecies structure, a feature shared with most other RNA viruses and retroviruses (7, 11, 18, 19, 31-36, 40, 43, 53, 59, 67, 68).…”

An investigation of the genetic basis of increased susceptibility to neutralization by anti-fusion glycoprotein antibody arising on passage of human respiratory syncytial virus in cell culture

“…Cell culture adaptation of virus leading to increase in sensitivity to in vitro neutralization has been reported in a number of viruses including HIV‐1, SIV, and FMDV [Gonzalez et al, ; Sullivan et al, ; Means et al, ]. Marsh et al [] reported a similar phenomenon for hRSV.…”