Das neu entdeckte „atypische porzine Pestivirus“ (APPV): ein alter Akteur im „Zitterferkelkrankheit“-Komplex?

Postel, Alexander; Becher, Paul; Haas, Ludwig; Wendt, Michael

doi:10.15653/tpg-180053

Cited by 4 publications

(3 citation statements)

References 40 publications

(84 reference statements)

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“…Soon thereafter, the virus was linked to congenital tremor type AII in piglets by Arruda et al [5] and others [2,3,6]. Since then, the virus has been described in a variety of countries, indicating that APPV is distributed worldwide [4,28,29]. In Switzerland, the first report of APPV in a sample from swine was found in a nasal swab analyzed by NGS by C. Bachofen in another project unrelated to pestiviruses (see Section 1).…”

Section: Discussionmentioning

confidence: 99%

“…However, the duration of virus elimination in these pigs remains unknown. In addition, it was reported that several pigs with or without clinical signs of CT were still viremic at time of slaughter [2,3,4]. Therefore, the probability of finding virus-positive, older animals in breeding farms is expected to be rather low, as represented by the low prevalence in samples from 2018.…”

Section: Discussionmentioning

confidence: 99%

“…Type A CT is further subclassified into five groups: type AIII and AIV are heritable forms in certain pig breeds and type AV is induced by intoxication with organophosphorus compounds during gestation, and both types, AI and AII, have infectious causes. Whereas type AI is caused by transplacental infection with classical swine fever virus (CSFV), the etiology of type AII was unclear for decades [1,2,3,4]. Only recently, CT type AII was linked to congenital infection with atypical porcine pestivirus (APPV) [2,3,5,6], a pestivirus that was discovered quite recently by metagenomic sequencing of porcine sera within a project on porcine reproductive and respiratory syndrome virus (PRRSV) [7].…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Circulation of Atypical Porcine Pestivirus (APPV) within Switzerland

Kaufmann

Stalder

Sidler

et al. 2019

Viruses

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In 2015, a new pestivirus was described in pig sera in the United States. This new “atypical porcine pestivirus” (APPV) was later associated with congenital tremor (CT) in newborn piglets. The virus appears to be distributed worldwide, but the limited knowledge of virus diversity and the use of various diagnostic tests prevent direct comparisons. Therefore, we developed an APPV-specific real-time RT-PCR assay in the 5′UTR of the viral genome to investigate both retro- and prospectively the strains present in Switzerland and their prevalence in domestic pigs. Overall, 1080 sera obtained between 1986 and 2018 were analyzed, revealing a virus prevalence of approximately 13% in pigs for slaughter, whereas it was less than 1% in breeding pigs. In the prospective study, APPV was also detected in piglets displaying CT. None of the samples could detect the Linda virus, which is another new pestivirus recently reported in Austria. Sequencing and phylogenetic analysis revealed a broad diversity of APP viruses in Switzerland that are considerably distinct from sequences reported from other isolates in Europe and overseas. This study indicates that APPV has already been widely circulating in Switzerland for many years, mainly in young animals, with 1986 being the earliest report of APPV worldwide.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-Term Circulation of Atypical Porcine Pestivirus (APPV) within Switzerland

Kaufmann

Stalder

Sidler

et al. 2019

Viruses

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Seroprevalence of atypical porcine pestivirus in a closed pig herd with subclinical infection

Grahofer

Zeeh

2020

Transbound. Emerg. Dis.

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Pestiviruses are highly variable RNA viruses within the family Flaviviridae and include several viruses causing major economic impacts, such as bovine viral diarrhoea viruses 1 and 2, border disease virus and classical swine fever virus (CSFV) (Cagatay et al., 2018). In 2015, a new pestivirus, named Atypical Porcine Pestivirus (APPV), was identified in healthy pigs (Hause et al., 2015). Thereafter, in two independent studies, an association of APPV with the clinical syndrome of congenital tremor was reported (Arruda et al., 2016; Postel et al., 2016).

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CRISPR/Cas9-Mediated Knockout of DNAJC14 Verifies This Chaperone as a Pivotal Host Factor for RNA Replication of Pestiviruses

Isken¹,

Postel

Bruhn³

et al. 2019

J Virol

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Pestiviruses like bovine viral diarrhea virus (BVDV) are a threat to livestock. For pestiviruses, cytopathogenic (cp) and noncytopathogenic (noncp) strains are distinguished in cell culture. The noncp biotype of BVDV is capable of establishing persistent infections, which is a major problem in disease control. The noncp biotype rests on temporal control of viral RNA replication, mediated by regulated cleavage of nonstructural protein 2-3 (NS2-3). This cleavage is catalyzed by the autoprotease in NS2, the activity of which depends on its cellular cofactor, DNAJC14. Since this chaperone is available in small amounts and binds tightly to NS2, NS2-3 translated later in infection is no longer cleaved. As NS3 is an essential constituent of the viral replicase, this shift in polyprotein processing correlates with downregulation of RNA replication. In contrast, cp BVDV strains arising mostly by RNA recombination show highly variable genome structures and display unrestricted NS3 release. The functional importance of DNAJC14 for noncp pestiviruses has been established so far only for BVDV-1. It was therefore enigmatic whether replication of other noncp pestiviruses is also DNAJC14 dependent. By generating bovine and porcine DNAJC14 knockout cells, we could show that (i) replication of 6 distinct noncp pestivirus species (A to D, F, and G) depends on DNAJC14, (ii) the pestiviral replicase NS3-5B can assemble into functional complexes in the absence of DNAJC14, and (iii) all cp pestiviruses replicate their RNA and generate infectious progeny independent of host DNAJC14. Together, these findings confirm DNAJC14 as a pivotal cellular cofactor for the replication and maintenance of the noncp biotype of pestiviruses. IMPORTANCE Only noncp pestivirus strains are capable of establishing life-long persistent infections to generate the virus reservoir in the field. The molecular basis for this biotype is only partially understood and only investigated in depth for BVDV-1 strains. Temporal control of viral RNA replication correlates with the noncp biotype and is mediated by limiting amounts of cellular DNAJC14 that activate the viral NS2 protease to catalyze the release of the essential replicase component NS3. Here, we demonstrate that several species of noncp pestiviruses depend on DNAJC14 for their RNA replication. Moreover, all cp pestiviruses, in sharp contrast to their noncp counterparts, replicate independently of DNAJC14. The generation of a cp BVDV in the persistently infected animal is causative for onset of mucosal disease. Therefore, the observed strict biotype-specific difference in DNAJC14 dependency should be further examined for its role in cell type/tissue tropism and the pathogenesis of this lethal disease.

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Das neu entdeckte „atypische porzine Pestivirus“ (APPV): ein alter Akteur im „Zitterferkelkrankheit“-Komplex?

Cited by 4 publications

References 40 publications

Long-Term Circulation of Atypical Porcine Pestivirus (APPV) within Switzerland

Long-Term Circulation of Atypical Porcine Pestivirus (APPV) within Switzerland

Seroprevalence of atypical porcine pestivirus in a closed pig herd with subclinical infection

CRISPR/Cas9-Mediated Knockout of DNAJC14 Verifies This Chaperone as a Pivotal Host Factor for RNA Replication of Pestiviruses

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