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

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.