E2 is one of the envelope
glycoproteins of pestiviruses, including classical swine fever virus (CSFV) and bovine viral
diarrhea virus (BVDV). E2 is involved in several critical functions, including virus entry into target cells, induction of a protective immune response and virulence in swine. However, there is no information regarding any host binding partners for the E2
proteins. Here, we utilized the yeast two-hybrid system and identified fifty-seven host
proteins as positive binding partners which bound E2 from both CSFV and BVDV with the exception of two
proteins that were found to be positive for binding only to CSFV E2.
Alanine scanning of CSFV E2 demonstrated that the binding sites for these cellular
proteins on E2 are likely non-linear binding sites. The possible roles of the identified host
proteins are discussed as the results presented here will be important for future studies to elucidate mechanisms of host
protein-virus interactions during
pestivirus infection. However, due to the limitations of the yeast two hybrid system, the
proteins identified is not exhaustive and each interaction identified needs to be confirmed by independent experimental approaches in the context of virus-infected cells before any definitive conclusion can be drawn on relevance for the virus life cycle.