title: Inhibition of replication of porcine reproductive and respiratory syndrome virus by hemin is highly dependent on heme oxygenase-1, but independent of iron in MARC-145 cells.
abstract: Current vaccines against porcine reproductive and respiratory syndrome virus (PRRSV) have failed to provide sustainable disease control, and development of new antiviral strategies is of great importance. The present study investigated the mechanism of the antiviral effect of hemin during PRRSV infection in MARC-145 cells. Hemin, a commercial preparation of heme, is used as an iron donor or heme oxygenase 1 (HO-1) inducer, and has been shown to provide antiviral activity in many studies. In the current study, the anti-PRRSV activity of hemin was identified through suppressing PRRSV propagation. The 50% inhibitory concentration (IC50) of hemin antiviral activity was estimated to be 32μM, and the 50% cytotoxic concentration (CC50) of hemin was found to be higher than 125μM. Further study showed that the antiviral activity of hemin is independent of iron. In addition, after treatment with Protoporphyrin IX zinc (II) (ZnPP) or Sn (IV) Protoporphyrin IX dichloride (SnPP), inhibitors of HO-1, the inhibition of viral replication by hemin was partially reversed. Additionally, it was confirmed that hemin and N-acetyl cysteine were able to significantly reduce reactive oxygen species (ROS) in MARC-145 cells infected with virus. N-acetyl-L-cysteine (NAC), however, did not produce a reduction in viral load or promote expression of HO-1. Taken together, these data indicate that the effect of hemin on the inhibition of PRRSV propagation via HO-1 induction, as well as the antiviral mechanism of HO-1, is not dependent on decreased levels of ROS. In conclusion, these data demonstrate that hemin had antiviral activity against PRRSV and may serve as a useful antiviral agent inhibiting PRRSV replication.
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Shuqi
authors.initials: S
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Meirui
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Guangyin
authors.initials: G
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Delin
authors.initials: D
authors.lastname: Mo
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: chyaosh@mail.sysu.edu.cn.
authors.forename: Yaosheng
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D002460:Cell Line; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D007501:Iron / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D019316:Porcine respiratory and reproductive syndrome virus / Q000187:drug effects* / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000032:analysis; D013552:Swine; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D017382:Reactive Oxygen Species; D006427:Hemin; D007501:Iron; D051547:Heme Oxygenase-1
keywords: Heme oxygenase-1; Hemin; Iron; PRRSV; ROS