In:
Journal of Virology, American Society for Microbiology, Vol. 95, No. 9 ( 2021-04-12)
Kurzfassung:
Pestiviruses such as bovine viral diarrhea virus (BVDV) and classical swine fever virus (CSFV) belong to the family Flaviviridae and represent pathogens of outstanding veterinary relevance. Pestiviruses enter cells via receptor-mediated endocytosis. For entry in bovine cells, complement regulatory protein CD46 bov serves as a cellular receptor for BVDV. In this study, the role of porcine CD46 pig in cellular entry was investigated for the recently discovered atypical porcine pestivirus (APPV), CSFV, and Bungowannah virus (BuPV) in order to elucidate the observed differences in host cell tropism. A cell culture-adapted APPV variant, which shows enhanced viral replication in vitro , was generated and demonstrated a strict tropism of APPV for porcine cells. One of the porcine cell lines displayed areas of CD46 pig -expressing cells and areas of nonexpressing cells, and one single cell line revealed not to express any CD46 pig . The CD46 pig -deficient porcine lymphoma cell line, known to facilitate CSFV replication, was the only porcine cell line nonpermissive to APPV, indicating a significant difference in the entry mechanism of APPV and CSFV. Infection experiments with a set of genetically engineered CD46 pig knockout cells confirmed that CD46 pig is a major receptor of APPV as CD46 bov is for BVDV. In contrast, it is apparently not an essential determinant in host cell entry of other porcine pestiviruses such as CSFV and BuPV. Existence of a CD46 pig -independent entry mechanism illustrates that the pestiviral entry process is more diverse than previously recognized. IMPORTANCE Pestiviruses comprise animal pathogens such as classical swine fever virus (CSFV) and bovine viral diarrhea virus (BVDV) that cause notifiable diseases with great economic impact. Several additional pestivirus species affecting animal health were recently identified, including atypical porcine pestivirus (APPV). APPV is associated with health problems in piglets and is highly abundant in pig populations worldwide. Complement control protein CD46 serves as a receptor for diverse bacterial and viral pathogens, including particular adenoviruses, herpesviruses, measles virus (MeV), and BVDV. Porcine CD46 (CD46 pig ) was suggested to be a major receptor for CSFV. Here, we identified remarkable differences in relevance of CD46 pig during entry of porcine pestiviruses. Resembling BVDV, efficient APPV infection in cell culture depends on CD46 pig , while other porcine pestiviruses can efficiently enter and infect cells in the absence of CD46 pig . Thus, the study provides insights into the entry process of these pathogens and may help to understand differences in their biology.
Materialart:
Online-Ressource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.02186-20
Sprache:
Englisch
Verlag:
American Society for Microbiology
Publikationsdatum:
2021
ZDB Id:
1495529-5
