title: Porcine complement regulatory protein CD46 and heparan sulfates are the major factors for classical swine fever virus attachment in vitro.
abstract: Classical swine fever virus (CSFV) is the causative agent of a severe multi-systemic disease of pigs. While several aspects of virus-host-interaction are known, the early steps of infection remain unclear. For the closely related bovine viral diarrhea virus (BVDV), a cellular receptor is known: bovine complement regulatory protein CD46. Given that these two pestiviruses are closely related, porcine CD46 is also a candidate receptor for CSFV. In addition to CD46, cell-culture-adapted CSFV strains have been shown to use heparan sulfates as an additional cellular factor. In the present study, the interaction of field-type and cell-culture-adapted CSFV with a permanent porcine cell line or primary macrophages was assessed using anti-porcine CD46 monoclonal antibodies and a heparan-sulfate-blocking compound, DSTP-27. The influence of receptor blocking was assessed using virus titration and quantitative PCR. Treatment of cells with monoclonal antibodies against porcine CD46 led to a reduction of viral growth in both cell types. The effect was most pronounced with field-type CSFV. The blocking could be enhanced by addition of DSTP-27, especially for cell-culture-adapted CSFV. The combined use of both blocking agents led to a significant reduction of viral growth but was also not able to abolish infection completely. The results obtained in this study showed that both porcine CD46 and heparan sulfates play a major role in the initial steps of CSFV infection. Additional receptors might also play a role for attachment and entry; however, their impact is obviously limited in vitro in comparison to CD46 and heparan sulfates.
authors.affiliation: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Suedufer 10, 17493, Greifswald, Insel Riems, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Dräger
authors.forename: Martin
authors.initials: M
authors.lastname: Beer
authors.forename: Sandra
authors.initials: S
authors.lastname: Blome
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006692:Classical Swine Fever Virus / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism*; D051916:Membrane Cofactor Protein / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011991:Receptors, Virus / Q000378:metabolism*; D013552:Swine; D019562:Viral Load; D053585:Virus Attachment
chemical_list: D006497:Heparan Sulfate; D051916:Membrane Cofactor Protein; D011991:Receptors, Virus