Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus

Abstract

Viruses can evolve to respond to immune pressures conferred by specific antibodies generated after vaccination and/or infection. In this study, an in vitro system was developed to investigate the impact of serum-neutralising antibodies upon the evolution of a foot-and-mouth disease virus (FMDV) isolate. The presence of sub-neutralising dilutions of specific antisera delayed the onset of virus-induced cytopathic effect (CPE) by up to 44 h compared to the untreated control cultures. Continued virus passage with sub-neutralising dilutions of these sera resulted in a decrease in time to complete CPE, suggesting that FMDV in these cultures adapted to escape immune pressure. These phenotypic changes were associated with three separate consensus-level non-synonymous mutations that accrued in the viral RNA-encoding amino acids at positions VP266, VP280 and VP1155, corresponding to known epitope sites. High-throughput sequencing also identified further nucleotide substitutions within the regions encoding the leader (Lpro), VP4, VP2 and VP3 proteins. While association of the later mutations with the adaptation to immune pressure must be further verified, these results highlight the multiple routes by which FMDV populations can escape neutralising antibodies and support the application of a simple in vitro approach to assess the impact of the humoral immune system on the evolution of FMDV and potentially other viruses.

Detection and Genetic Analysis of Bovine Rhinitis B Virus in Japan

“…The functions of VP1 and VP2 in BRBV remain unexplored; however, these proteins have been characterized in FMDV and may be related to antigenicity [22]. Certain amino acid mutations in VP1 and VP2 of FMDV reportedly cause immune evasion [22], suggesting that similar mutations in these two proteins of LAV/238002 are involved in immune escape. In IBA/2211/2, 2B protein had an amino acid deletion (1121E) identical to the Chinese strain SC1_LZ02 [11], whereas LAV/238002 exhibited a different deletion (1117DG) nearby.…”

“…In LAV/238002, 10 mutations were found in VP1, VP2, and VP3 proteins, which form the outer surface of the capsid and contain major neutralizing sites [18][19][20][21]. The functions of VP1 and VP2 in BRBV remain unexplored; however, these proteins have been characterized in FMDV and may be related to antigenicity [22]. Certain amino acid mutations in VP1 and VP2 of FMDV reportedly cause immune evasion [22], suggesting that similar mutations in these two proteins of LAV/238002 are involved in immune escape.…”

Detection and Genomic Characterization of Bovine Rhinitis Virus in China

“…Among these aa mutations, 19 mutations were located in the VP1, VP2, and VP3 proteins that make up the outer surface of the capsid [11,29] and contain major neutralizing sites [30,31]. Up to now, functions of VP1 and VP2 remain undetermined in BRV, while they have been well-studied in foot-andmouth disease virus (FMDV), another well-known member of Aphthoviruses, and they are presumed to be related to antigenicity [32].The certain aa mutations in VP1 and VP2 are reported to cause immune escape of FMDV [32], and therefore it is reasonably speculated that the unique aa mutations in these two proteins of SC1_LZ02 might also cause immune escape, suggesting the importance of monitoring such BRV mutants. Interestingly, aa deletions were observed in VP2 (431VKE and 496IH) and VP3 (595G) of SC1_LZ05, which also presented in corresponding regions of FMDV type SAT2 (GenBank: MW715628.1), suggesting that aa deletion of structural proteins might play an important role in the evolution of Aphthoviruses.…”

Correction: King et al. Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus. Viruses 2022, 14, 1820

“…In the original publication [ 1 ], Figure 4 and the corresponding legend were missing. The added Figure 4 , showing surface-exposed non-synonymous mutations, appears below.…”