Hsp90 inhibitor reduces porcine circovirus 2 replication in the porcine monocytic line 3D4/31.

Porcine circovirus 2 (PCV2) is an important pathogen of swine, which causes porcine circovirus disease and porcine circovirus-associated diseases (PCVD/PCVAD). However, no effective countermeasures exist to combat this virus infection so far. Recently, heat shock protein 90 (Hsp90) was found to be an important host factor for the replication of multiple viruses and the inhibition of Hsp90 showed significant antiviral effects. Inhibition of Hsp90 by treatment of porcine monocytic line 3D4/31 with geldanamycin (GA), a specific inhibitor of Hsp90, caused a 70 % decrease in viral Cap protein expression. Further, individual knockdown targeting Hsp90α or Hsp90β with siRNAs resulted in down to 20-25 % of decrease in viral replication, and inhibited the PCV2 titer by approximately 12- and 15-fold, respectively. In addition, we investigated alteration of several cytokine production in PCV2-infected cells following treatment with GA. Then, we found that GA could decrease IL-1β, IL-6, and IL-12p40 mRNA levels, respectively, by 30, 40, and 40 % in PCV2-infected cells. Our results shed light on the possibility of developing potential therapeutics targeting Hsp90 against PCV2 infection.