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Fosfomycin modifies the replication kinetics of bovine alphaherpesvirus-1 and reduces the timing of its protein expression on bovine (MDBK) and human (SH-SY5Y) cell lines

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Abstract

Bovine alphaherpesvirus 1 (BoAHV-1) predisposes cattle to respiratory secondary bacterial infections, which can be treated with the broad-spectrum antibiotic fosfomycin. This drug also suppresses NF-kB activity and pro-inflammatory responses. Therefore, cattle may be exposed to an interaction between the virus and the antibiotic which may have effects on it. The aim of this study was to determine the effect of calcium fosfomycin (580 µg/mL) on BoAHV-1 (moi = 0.1) replication. Two cell lines (MDBK and SH-SY5Y) were used in this study. Our results show that fosfomycin has novel properties. By MTT assay we have shown that it is non-cytotoxic for any of the cell lines. Extracellular and intracellular viral titers demonstrated that fosfomycin has a cell-type and time-dependent effect on BoAHV-1 replication. By direct immunofluorescence it was shown that it reduces the timing of BoAHV-1 protein expression, and by qPCR, we found that its effect on NF-kB mRNA expression depends on the cell type.

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Funding

This work was supported by the Secretaría de Ciencia, Arte y Tecnología de la Universidad Nacional del Centro de la Provincia de Buenos Aires (SECAT-UNCPBA) (Grant 03-JOVIN-77 H).

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Authors and Affiliations

  1. Lab. de Toxicología, Depto. de Fisiopatología, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET-UNCPBA, Tandil, Bs. As, Argentina

    Denisa Pérez Gaudio, Guadalupe Martínez, Julieta Decundo, Susana Dieguez & Alejandro Soraci

  2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bs. As, Argentina

    Denisa Pérez Gaudio, Guadalupe Martínez, Julieta Decundo & Alejandro Soraci

  3. Lab. de Virología, Depto. de Sanidad Animal y Medicina Preventiva, Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET-UNCPBA, Tandil, Bs. As, Argentina

    Sandra Pérez

  4. Actividad privada, Tandil, Bs. As, Argentina

    Joaquín Mozo

  5. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), Bs. As, La Plata, Argentina

    Susana Dieguez

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  1. Denisa Pérez Gaudio
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Contributions

D.P.G. had the original idea, performed the assays and wrote the manuscript. S.P. performed the assays and wrote the article. J.M., G.M., J.D., S.D and A.S. collaborated on the assays. J.M. and J.D. performed the statistical analysis. All authors reviewed the manuscript.

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Correspondence to Denisa Pérez Gaudio.

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Pérez Gaudio, D., Pérez, S., Mozo, J. et al. Fosfomycin modifies the replication kinetics of bovine alphaherpesvirus-1 and reduces the timing of its protein expression on bovine (MDBK) and human (SH-SY5Y) cell lines. Vet Res Commun 47, 1963–1972 (2023). https://doi.org/10.1007/s11259-023-10150-w

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