Leaderless foot-and-mouth disease virus serotype O did not cause clinical disease and failed to establish a persistent infection in cattle

Benedikt Litz ¹, Julia Sehl-Ewert ², Angele Breithaupt ²

⁰Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.

Emerging Microbes & Infections +

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April 29, 2024

View abstract on PubMed

Summary

Foot-and-mouth disease virus (FMDV) lacking the L<sup>pro</sup> proteinase cannot establish acute infection or persistent infection in cattle. This leaderless FMDV variant demonstrated significant attenuation in vivo, highlighting the L<sup>pro</sup> proteinase

Area Of Science

Virology
Immunology
Veterinary Medicine

Background

Foot-and-mouth disease virus (FMDV) Leader proteinase L<sup>pro</sup> is crucial for inhibiting host mRNA translation and blocking interferon responses, aiding viral survival.
While L<sup>pro</sup> is dispensable for in vitro viral replication, FMDV serotype A lacking L<sup>pro</sup> shows attenuation in cattle and pigs.
The capacity of leaderless FMDV to establish persistent infections in vivo and the consistency of attenuation across serotypes remain uncharacterized.

Purpose Of The Study

To investigate whether a foot-and-mouth disease virus (FMDV) O/FRA/1/2001 variant lacking the L<sup>pro</sup> proteinase (ΔLb) can establish persistent infection in vivo following simulated natural infection.
To determine if the O/FRA/1/2001 ΔLb variant exhibits attenuation during the acute phase of infection in cattle.
To assess the potential for persistent infection of the upper respiratory tract by the leaderless FMDV variant in a bovine model.

Main Methods

Generation of an FMDV O/FRA/1/2001 variant (ΔLb) with a deletion in the L<sup>pro</sup> coding region.
Intranasopharyngeal inoculation of cattle with the FMDV O/FRA/1/2001 ΔLb variant.
Observation of inoculated cattle for 35 days to monitor for signs of acute infection, viral shedding, and persistent infection in pharyngeal tissues.

Main Results

The leaderless FMDV O/FRA/1/2001 ΔLb variant replicated in vitro in various cell lines.
In vivo, the FMDV O/FRA/1/2001 ΔLb variant failed to establish acute infection, characterized by a lack of vesicular lesions and viral shedding in cattle.
The leaderless FMDV variant was unable to establish persistent infection in the bovine pharyngeal tissues.

Conclusions

The FMDV L<sup>pro</sup> proteinase is essential for establishing acute infection and viral shedding in cattle.
Leaderless FMDV variants are significantly attenuated and incapable of causing persistent infections in the bovine upper respiratory tract.
The absence of L<sup>pro</sup> prevents both acute disease and long-term colonization, underscoring its role in FMDV pathogenesis.

Keywords:

FMDV Foot-and-mouth disease virus carrier leader proteinase persistence