Foot-and-Mouth Disease Virus: Molecular Interplays with IFN Response and the Importance of the Model

Abstract

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals with a significant socioeconomic impact. One of the issues related to this disease is the ability of its etiological agent, foot-and-mouth disease virus (FMDV), to persist in the organism of its hosts via underlying mechanisms that remain to be elucidated. The establishment of a virus–host equilibrium via protein–protein interactions could contribute to explaining these phenomena. FMDV has indeed developed numerous strategies to evade the immune response, especially the type I interferon response. Viral proteins target this innate antiviral response at different levels, ranging from blocking the detection of viral RNAs to inhibiting the expression of ISGs. The large diversity of impacts of these interactions must be considered in the light of the in vitro models that have been used to demonstrate them, some being sometimes far from biological systems. In this review, we have therefore listed the interactions between FMDV and the interferon response as exhaustively as possible, focusing on both their biological effect and the study models used.

Host-Specific Interplay between Foot-and-Mouth Disease Virus 3D Polymerase and the Type-I Interferon Pathway

“…In view of the results obtained during our screening, it seems relevant to consider the importance of the models used for the identification of PPI, since some of them do not seem to be conserved from one species to another. This problem seems all the more important as a large proportion of the PPI identified were obtained with expressed proteins that were not derived from species sensitive to FMD, such as humans, a species that is not necessarily the most suitable for studying a virus affecting artiodactyls [ 26 ]. Furthermore, it seems that other variables also have a role to play.…”

“…Moreover, it is possible that not all these interactions are involved in blocking the IFN pathway. On the other hand, if we put ourselves in the global context of infection, FMDV is known to involve almost all of its proteins in fighting against the host cellular response [ 21 , 25 , 26 ]. It would thus seem to be logical that each protein is not capable, by itself, of inducing a strong inhibition of the immune response, but that the subversion of the immune response induced by FMDV is due to a synergic action between the different viral proteins.…”

“…Similarly, after having long been side-lined in favour of their importance in viral structure, the impact of FMDV structural proteins in fighting the immune system has recently been shown to be much more important than the scientific community had thought. More generally, the large number of studies on FMDV-associated PPI show that this virus dedicates almost its entire small genome to fighting the immune system and especially the type-I interferon pathway [ 26 , 65 ].…”

“…This inhibitory effect could be related to its ability to interact in vitro with numerous IFN pathway proteins derived from cattle, sheep, goat and swine, namely, IKKα, IKKε, IRF3, IRF7, MDA5 and NEMO, as well as with the swine version of MAVS (represented by 3D*). Adapted from Sarry et al [ 26 ]. Created with (accessed on 11 October 2022).…”

“…Numerous interactions have been identified between FMDV proteins and cellular proteins involved in the innate immune responses of its different hosts. Several reviews have also been written to list these interactions [ 21 , 25 , 26 ]. According to these reviews, it appears that not all viral proteins are equally important in viral escape from the host’s antiviral action.…”