title: Hsp90 inhibitor reduces porcine circovirus 2 replication in the porcine monocytic line 3D4/31.
abstract: 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.
authors.affiliation: Department of Comparative Medicine, Jinling Hospital, 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Comparative Medicine, Jinling Hospital, 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China.
authors.forename: Xuliang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Comparative Medicine, Jinling Hospital, 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Ma
authors.affiliation: Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of Comparative Medicine, Jinling Hospital, 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China. ysf_nj@126.com.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Yun
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D018173:Circoviridae Infections / Q000662:veterinary; D017925:Circovirus / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D013552:Swine; D013553:Swine Diseases / Q000235:genetics / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D018841:HSP90 Heat-Shock Proteins
keywords: Antiviral; Geldanamycin; Hsp90; Porcine circovirus type 2