Annexin A2 associates to feline calicivirus RNA in the replication complexes from infected cells and participates in an efficient viral replication

•AnexA2 is in vitro associated with the 3′UTR from the FCV RNA.•AnxA2 is associated with the viral RNA in the replication complexes from FCV.•AnxA2-knockdown causes a reduction in FCV protein and dsRNA production.•AnxA2-knockdown causes a decrease of FCV production.•AnxA2 is required for an efficient FCV production. Cellular proteins have been identified to participate in calicivirus replication in association with viral proteins and/or viral RNAs. By mass spectrometry from pull-down assays, we identified several cellular proteins bound to the feline calicivirus (FCV) genomic RNA; among them the lipid raft-associated scaffold protein Annexin (Anx) A2. AnxA2 colocalizes with FCV NS6/7 protein and with the dsRNA in infected cells; moreover, it was found associated with the viral RNA in the membrane fraction corresponding to the replication complexes (RCs), suggesting its role during FCV replication. AnxA2-knockdown from CrFK cells prior to infection with FCV caused a delay in the cytopathic effect, a strong reduction of viral non-structural proteins and dsRNA production, and a decrease of FCV yield in both cell-associated and supernatant fractions. Taken together, these results indicate that AnxA2 associates to the genomic RNA of FCV and is required for an efficient FCV replication.