biostudies-literatureReuscher CMDeutsche Forschungsgemeinschafte0198021https://www.ebi.ac.uk/biostudies/studies/S-EPMC9364808biostudies-literatureUnknown96(15)Atypical porcine pestiviruses (APPV; <i>Pestivirus K</i>) are a recently discovered, very divergent species of the genus <i>Pestivirus</i> within the family <i>Flaviviridae</i>. The presence of APPV in piglet-producing farms is associated with the occurrence of so-called "shaking piglets," suffering from mild to severe congenital tremor type A-II. Previous studies showed that the cellular protein DNAJC14 is an essential cofactor of the NS2 autoprotease of all classical pestiviruses. Consequently, genetically engineered DNAJC14 knockout cell lines were resistant to all tested noncytopathogenic (non-cp) pestiviruses. Surprisingly, we found that the non-cp APPV can replicate in these cells in the absence of DNAJC14, suggesting a divergent mechanism of polyprotein processing. A complete laboraJournal of virologyDNAJC14-Independent Replication of the Atypical Porcine Pestivirus.PMC9364808197785619Zimmer KLamp BBarth STautz NRaigel MReuscher CMHuber TIsken OGeranio FSeitz KRiedel CNetsch ARumenapf TSchwarz LfalseDNAJC14-Independent Replication of the Atypical Porcine Pestivirus.Atypical porcine pestiviruses (APPV; <i>Pestivirus K</i>) are a recently discovered, very divergent species of the genus <i>Pestivirus</i> within the family <i>Flaviviridae</i>. The presence of APPV in piglet-producing farms is associated with the occurrence of so-called "shaking piglets," suffering from mild to severe congenital tremor type A-II. Previous studies showed that the cellular protein DNAJC14 is an essential cofactor of the NS2 autoprotease of all classical pestiviruses. Consequently, genetically engineered DNAJC14 knockout cell lines were resistant to all tested noncytopathogenic (non-cp) pestiviruses. Surprisingly, we found that the non-cp APPV can replicate in these cells in the absence of DNAJC14, suggesting a divergent mechanism of polyprotein processing. A complete labora2022-01-01T00:00:00Z2022 Aug2025-04-04T08:01:31.746Z2025-04-04T08:01:31.746ZS-EPMC93648083585235210.1128/jvi.01980-21