|Diaz-san Segundo, Fayna|
|De Los Santos, Teresa|
Submitted to: Federation of European Microbiological Societies Microbiology Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/13/2008
Publication Date: 4/9/2008
Citation: Grubman, M.J., Moraes, M., Diaz-San Segundo, F., Pena, L., De Los Santos, T. 2008. Evading the Host Immune Response: How Foot-and-Mouth Disease Virus Has Become an Effective Pathogen. Federation of European Microbiological Societies Microbiology Letters. 53:8-17. Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of cloven-hoofed animals. To develop improved strategies needed to control this disease it is important to understand how the virus and the host interact. Identification of mechanisms that the host can utilize to rapidly control and contain virus replication may result in disease control approaches that are able to augment current and potential vaccine strategies. In this review we provide a brief overview of foot-and-mouth disease, the economic impact of outbreaks in previously disease-free countries, and a description of the viral encoded structural and nonstructural proteins. We then, in some detail, discuss what is currently known about host processes and protective immune responses that FMDV subverts and the molecular mechanisms and viral proteins that are involved.
Technical Abstract: Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of cloven-hoofed animals. In this review we discuss the mechanisms FMDV has evolved to counteract or block both the host innate and adaptive immune responses allowing it to become such a successful pathogen. The role of a number of viral proteins in this process is examined. The viral leader proteinase, Lpro, plays an important role in limiting the host innate response to virus infection by inhibiting the induction of interferon beta mRNA and blocking host cell translation. There is evidence that a second viral proteinase, 3Cpro, may affect host cell transcription because it cleaves histone H3. Viral protein 2B in conjunction with 2C or their precursor 2BC inhibit protein trafficking through the endoplasmic reticulum and Golgi apparatus. A decrease in surface expression of the major histocompatibility class I molecules during FMDV infection suggests that these viral proteins may be involved in delaying the initiation of the host adaptive immune response and may also adversely affect the secretion of induced signaling molecules including cytokines and chemokines. In addition, FMDV causes a transient lymphopenia in swine, but the mechanism involved in this process is not understood nor have any viral protein(s) been implicated. Furthermore, the interaction of FMDV with various cells in the immune system including lymphocytes and dendritic cells and the possible role of apoptosis and autophagy with respect to these interactions are discussed.