PMID- 24583029 OWN - NLM STAT- MEDLINE DCOM- 20141201 LR - 20161125 IS - 1872-9096 (Electronic) IS - 0166-3542 (Linking) VI - 105 DP - 2014 May TI - 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. PG - 39-46 LID - S0166-3542(14)00053-9 [pii] LID - 10.1016/j.antiviral.2014.02.010 [doi] AB - 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 32muM, and the 50% cytotoxic concentration (CC50) of hemin was found to be higher than 125muM. 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. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Wang, Liangliang AU - Wang L AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. FAU - Xiao, Shuqi AU - Xiao S AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. FAU - Gao, Jintao AU - Gao J AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. FAU - Liu, Meirui AU - Liu M AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. FAU - Zhang, Xiaoyu AU - Zhang X AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. FAU - Li, Ming AU - Li M AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. FAU - Zhao, Guangyin AU - Zhao G AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. FAU - Mo, Delin AU - Mo D AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. FAU - Liu, Xiaohong AU - Liu X AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. FAU - Chen, Yaosheng AU - Chen Y AD - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: chyaosh@mail.sysu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140225 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Antiviral Agents) RN - 0 (Reactive Oxygen Species) RN - 743LRP9S7N (Hemin) RN - E1UOL152H7 (Iron) RN - EC 1.14.14.18 (Heme Oxygenase-1) SB - IM MH - Animals MH - Antiviral Agents/*metabolism MH - Cell Line MH - Heme Oxygenase-1/*metabolism MH - Hemin/*metabolism MH - Inhibitory Concentration 50 MH - Iron/*metabolism MH - Microbial Sensitivity Tests MH - Porcine respiratory and reproductive syndrome virus/*drug effects/*physiology MH - Reactive Oxygen Species/analysis MH - Swine MH - Viral Load MH - Virus Replication/*drug effects OTO - NOTNLM OT - Heme oxygenase-1 OT - Hemin OT - Iron OT - PRRSV OT - ROS EDAT- 2014/03/04 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/03/04 06:00 PHST- 2013/11/03 00:00 [received] PHST- 2014/01/19 00:00 [revised] PHST- 2014/02/13 00:00 [accepted] PHST- 2014/03/04 06:00 [entrez] PHST- 2014/03/04 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - S0166-3542(14)00053-9 [pii] AID - 10.1016/j.antiviral.2014.02.010 [doi] PST - ppublish SO - Antiviral Res. 2014 May;105:39-46. doi: 10.1016/j.antiviral.2014.02.010. Epub 2014 Feb 25.