Heme Oxygenase-1 Suppresses Bovine Viral Diarrhoea Virus Replication in vitro

Zhang, Chong; Pu, Fengxing; Zhang, Angke; Xu, Liang; Li, Na; Yan, Yin; Gao, Jiming; Liu, Hongliang; Zhang, Gaiping; Goodfellow, Ian; Zhou, En‐Min; Xiao, Shuqi

doi:10.1038/srep15575

Cited by 18 publications

(15 citation statements)

References 30 publications

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“…Additionally, it also works as a strong negative regulator in the development of oxidative stress, which is upregulated by many signaling pathways7, and its protection has been confirmed in myocardial ischemia-reperfusion injury, hepatic injury, brain hemorrhage, acute kidney injury and viral diarrhea8. Our previous findings showed strong evidence that HO-1 upregulation plays a pivotal role in the defense against oxidative stress and acts as a critical mediator of cellular homeostasis.…”

mentioning

confidence: 75%

“…The induction of HO-1 occurs as an adaptive and beneficial response in many varied tissues and cellular injury models including sepsis, ischemia reperfusion, hyperoxia, hypoxia, and other oxidative stress28. Our previous studies also showed that the induction of HO-1 by LPS has a protective effect on the lung, kidney and liver8928. Recently, studies have shown that the mechanism is likely regulated via the NF-κB and Nrf2/HO-1 signaling pathway29.…”

Section: Discussionmentioning

confidence: 98%

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Effect of Heme Oxygenase-1 on Mitofusin-1 protein in LPS-induced ALI/ARDS in rats

Wang

et al. 2016

Sci Rep

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Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common and important oxidative stress in the lung. Mitochondrial fusion responds to the normal morphology and function of cells and is finely regulated by mitochondrial fusion proteins, such as mitofusin-1 protein (Mfn1), mitofusin-2 protein (Mfn2) and optical atrophy 1 (OPA1). Additionally, Mfn1 has been identified as the most important protein in mitochondrial fusion. Heme oxygenase-1 (HO-1) is a stress-inducible protein that plays a critical role in protecting against oxidative stress. However, whether the protection of HO-1 is related to mitochondrial fusion is still a question. Thus, our in vitro and in vivo experiments aimed to identify the relationship between HO-1 and Mfn1. Here, we used Hemin and ZnPP-IX as treatments in an in vivo experiment. Then, HO-1 and Mfn1 were measured using RT-PCR and Western blotting. Supernatants were analyzed for MDA, SOD, and ROS. Our results implied that HO-1 upregulation suppressed oxidative stress induced by LPS, and the possible mechanism could be associated with Mfn1 and the PI3K/Akt pathway.

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confidence: 75%

Section: Discussionmentioning

confidence: 98%

Effect of Heme Oxygenase-1 on Mitofusin-1 protein in LPS-induced ALI/ARDS in rats

Wang

et al. 2016

Sci Rep

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“…Enhanced HO-1 expression inhibits replication of many viruses, including HIV-1, Ebola virus, hepatitis B virus (HBV), and hepatitis C virus (HCV) (11)(12)(13)(14). Our previous work showed that overexpression or induction of HO-1 expression inhibits PRRSV and bovine viral diarrhea virus (BVDV) replication (15,16). Furthermore, microRNA miR-24-3p promotes PRRSV replication through suppression of HO-1 expression (17), indicating that increased expression of HO-1 may provide a potential new antiviral strategy against PRRSV infection.…”

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confidence: 99%

Carbon Monoxide Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by the Cyclic GMP/Protein Kinase G and NF-κB Signaling Pathway

Zhang

Zhao

et al. 2017

J Virol

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Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the pork industry worldwide each year. Our previous research demonstrated that heme oxygenase-1 (HO-1) can suppress PRRSV replication via an unknown molecular mechanism. In this study, inhibition of PRRSV replication was demonstrated to be mediated by carbon monoxide (CO), a downstream metabolite of HO-1. Using several approaches, we demonstrate that CO significantly inhibited PRRSV replication in both a PRRSV permissive cell line, MARC-145, and the predominant cell type targeted during in vivo PRRSV infection, porcine alveolar macrophages (PAMs). Our results showed that CO inhibited intercellular spread of PRRSV; however, it did not affect PRRSV entry into host cells. Furthermore, CO was found to suppress PRRSV replication via the activation of the cyclic GMP/protein kinase G (cGMP/PKG) signaling pathway. CO significantly inhibits PRRSV-induced NF-B activation, a required step for PRRSV replication. Moreover, CO significantly reduced PRRSV-induced proinflammatory cytokine mRNA levels. In conclusion, the present study demonstrates that CO exerts its anti-PRRSV effect by activating the cellular cGMP/PKG signaling pathway and by negatively regulating cellular NF-B signaling. These findings not only provide new insights into the molecular mechanism of HO-1 inhibition of PRRSV replication but also suggest potential new control measures for future PRRSV outbreaks.IMPORTANCE PRRSV causes great economic losses each year to the swine industry worldwide. Carbon monoxide (CO), a metabolite of HO-1, has been shown to have antimicrobial and antiviral activities in infected cells. Our previous research demonstrated that HO-1 can suppress PRRSV replication. Here we show that endogenous CO produced through HO-1 catalysis mediates the antiviral effect of HO-1. CO inhibits PRRSV replication by activating the cellular cGMP/PKG signaling pathway and by negatively regulating cellular NF-B signaling. These findings not only provide new insights into the molecular mechanism of HO-1 inhibition of PRRSV replication but also suggest potential new control measures for future PRRSV outbreaks.

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“…Heme oxygenase-1 (HO-1) breaks down heme to biliverdin, carbon monoxide (CO) and ferrous iron 13 . It has been reported that HO-1 can mediate cytoprotective effects under inflammatory conditions, and induction of HO-1 is thought to be an adaptive cellular response against stress 14 .…”

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confidence: 99%

Heme oxygenase-1 attenuates IL-1β induced alteration of anabolic and catabolic activities in intervertebral disc degeneration

Shi

et al. 2016

Sci Rep

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Intervertebral disc degeneration (IDD) is characterized by disordered extracellular matrix (ECM) metabolism, implicating subdued anabolism and enhanced catabolic activities in the nucleus pulposus (NP) of discs. Pro-inflammatory cytokines such as interleukin-1β (IL-1β) are considered to be potent mediators of ECM breakdown. Hemeoxygenase-1 (HO-1) has been reported to participate in cellular anti-inflammatory processes. The purpose of this study was to investigate HO-1 modulation of ECM metabolism in human NP cells under IL-1β stimulation. Our results revealed that expression of HO-1 decreased considerably during IDD progression. Induction of HO-1 by cobalt protoporphyrin IX attenuated the inhibition of sulfate glycosaminoglycan and collagen type II (COL-II) synthesis and ameliorated the reduced expressions of aggrecan, COL-II, SOX-6 and SOX-9 mediated by IL-1β. Induction of HO-1 also reversed the effect of IL-1β on expression of the catabolic markers matrix metalloproteinases-1, 3, 9 and 13. This was combined with inhibition of the activation of mitogen-activated protein kinase signaling. These findings suggest that HO-1 might play a pivotal role in IDD, and that manipulating HO-1 expression might mitigate the impairment of ECM metabolism in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD.

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Heme Oxygenase-1 Suppresses Bovine Viral Diarrhoea Virus Replication in vitro

Cited by 18 publications

References 30 publications

Effect of Heme Oxygenase-1 on Mitofusin-1 protein in LPS-induced ALI/ARDS in rats

Effect of Heme Oxygenase-1 on Mitofusin-1 protein in LPS-induced ALI/ARDS in rats

Carbon Monoxide Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by the Cyclic GMP/Protein Kinase G and NF-κB Signaling Pathway

Heme oxygenase-1 attenuates IL-1β induced alteration of anabolic and catabolic activities in intervertebral disc degeneration

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