Pathogenesis of wild-type and leaderless foot-and-mouth disease virus in cattle

Brown, Corrie C.; Piccone, María E.; Mason, Peter W.; McKenna, Thomas; Grubman, Marvin J.

doi:10.1128/jvi.70.8.5638-5641.1996

Cited by 102 publications

(53 citation statements)

References 16 publications

(21 reference statements)

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“…Several illuminating examples strongly suggest that security proteins can markedly modulate viral pathogenicity. FmDV lacking L is highly attenuated 89 , 132 . || For the viral genera with more than one species, the level of interspecies amino acid identity (and similarity, in parentheses) was calculated with the aid of CLUSTAL_X2 alignments, using utilities implemented in BioEdit and the BLOSUM62 similarity matrix 134 .…”

Section: Effects On Innate Immunity and Viral Pathogenicitymentioning

confidence: 99%

Viral security proteins: counteracting host defences

Agol

Gmyl

2010

Nat Rev Microbiol

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Interactions with host defences are key aspects of viral infection. Various viral proteins perform counter-defensive functions, but a distinct class, called security proteins, is dedicated specifically to counteracting host defences. Here, the properties of the picornavirus security proteins L and 2A are discussed. These proteins have well-defined positions in the viral polyprotein, flanking the capsid precursor, but they are structurally and biochemically unrelated. Here, we consider the impact of these two proteins, as well as that of a third security protein, L(*), on viral reproduction, pathogenicity and evolution. The concept of security proteins could serve as a paradigm for the dedicated counter-defensive proteins of other viruses.

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Section: Effects On Innate Immunity and Viral Pathogenicitymentioning

confidence: 99%

Viral security proteins: counteracting host defences

Agol

Gmyl

2010

Nat Rev Microbiol

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“…As expected, within vesicles, FMDV predominantly colocalized with CK confirming that FMDV-positive, CK-positive cells were keratinocytes (Figs. [3][4][5][6][7][8][9].…”

Section: Fluorescent Antibody Characterization Of Vesiclesmentioning

confidence: 99%

Optimization of Immunohistochemical and Fluorescent Antibody Techniques for Localization of Foot-and-Mouth Disease Virus in Animal Tissues

et al. 2009

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Immunohistochemical (IHC) and fluorescent antibody (FA) techniques were optimized for the detection of Foot-and-mouth disease virus (FMDV) structural and nonstructural proteins in frozen and paraformaldehyde-fixed, paraffin-embedded (PFPE) tissues of bovine and porcine origin. Immunohistochemical localization of FMDV was compared with 7 detection systems, 8 primary antibodies, and 11 epitope retrieval techniques. All serotypes tested (O, A, Asia, C [cryosection]; O, A, Asia [PFPE]) were localized in association with mature vesicles. Multi-label FA was used in conjunction with IHC and conventional histopathology to characterize vesicle maturation in 4 steers and 2 pigs experimentally infected with FMDV. At the edge of advancing vesicles, a consistent finding was acantholytic degeneration of basal keratinocytes surrounding dermal papillae with suprabasilar clefts and microvesiculation. Progression of microvesiculation led to coalescence with the expanding vesicle. Cells at the leading edge of vesicles were positive for FMDV antigens by IHC and FA. Cell marker profile of these cells by FA was consistent with keratinocytes (i.e., cytokeratin [CK]-positive, S100-negative, MHC-II-negative). In rare instances, CK-negative, MHC-II- positive, and FMDV-positive cells (presumptive dendritic cells or macrophages) were identified within dermis subjacent to vesicles.

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“…infection in vivo relies on L pro (30). Besides causing translational shutoff of host proteins, L pro suppresses the induction of IFN-␣/␤ (31).…”

mentioning

confidence: 99%

Foot-and-Mouth Disease Virus Leader Protease Cleaves G3BP1 and G3BP2 and Inhibits Stress Granule Formation

Visser

Medina

Rabouw

et al. 2019

J Virol

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Like other viruses, the picornavirus foot-and-mouth disease virus (FMDV; genus Aphthovirus), one of the most notorious pathogens in the global livestock industry, needs to navigate antiviral host responses to establish an infection. There is substantial insight into how FMDV suppresses the type I interferon (IFN) response, but it is largely unknown whether and how FMDV modulates the integrated stress response. Here, we show that the stress response is suppressed during FMDV infection. Using a chimeric recombinant encephalomyocarditis virus (EMCV), in which we functionally replaced the endogenous stress response antagonist by FMDV leader protease (L pro ) or 3C pro , we demonstrate an essential role for L pro in suppressing stress granule (SG) formation. Consistently, infection with a recombinant FMDV lacking L pro resulted in SG formation. Additionally, we show that L pro cleaves the known SG scaffold proteins G3BP1 and G3BP2 but not TIA-1. We demonstrate that the closely related equine rhinitis A virus (ERAV) L pro also cleaves G3BP1 and G3BP2 and also suppresses SG formation, indicating that these abilities are conserved among aphthoviruses. Neither FMDV nor ERAV L pro interfered with phosphorylation of RNAdependent protein kinase (PKR) or eIF2␣, indicating that L pro does not affect SG formation by inhibiting the PKR-triggered signaling cascade. Taken together, our data suggest that aphthoviruses actively target scaffolding proteins G3BP1 and G3BP2 and antagonize SG formation to modulate the integrated stress response. IMPORTANCE The picornavirus foot-and-mouth disease virus (FMDV) is a notorious animal pathogen that puts a major economic burden on the global livestock industry. Outbreaks have significant consequences for animal health and product safety. Like many other viruses, FMDV must manipulate antiviral host responses to establish infection. Upon infection, viral double-stranded RNA (dsRNA) is detected, which results in the activation of the RNA-dependent protein kinase (PKR)-mediated stress response, leading to a stop in cellular and viral translation and the formation of stress granules (SG), which are thought to have antiviral properties. Here, we show that FMDV can suppress SG formation via its leader protease (L pro ). Simultaneously, we observed that L pro can cleave the SG scaffolding proteins G3BP1 and G3BP2. Understanding the molecular mechanisms of the antiviral host response evasion strategies of FMDV may help to develop countermeasures to control FMDV infections in the future.

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Pathogenesis of wild-type and leaderless foot-and-mouth disease virus in cattle

Cited by 102 publications

References 16 publications

Viral security proteins: counteracting host defences

Viral security proteins: counteracting host defences

Optimization of Immunohistochemical and Fluorescent Antibody Techniques for Localization of Foot-and-Mouth Disease Virus in Animal Tissues

Foot-and-Mouth Disease Virus Leader Protease Cleaves G3BP1 and G3BP2 and Inhibits Stress Granule Formation

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