Cholesterol 25-hydroxylase is an interferon-inducible factor that protects against porcine reproductive and respiratory syndrome virus infection

Song, Zhongbao; Zhang, Qiaoya; Liu, Xuewei; Bai, Juan; Zhao, Yongxiang; Wang, Xianwei; Jiang, Ping

doi:10.1016/j.vetmic.2017.09.011

Cited by 41 publications

(34 citation statements)

References 34 publications

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“…A number of studies have illustrated that CH25H can be upregulated by some viruses, including HCV, PRRSV, and PRV (Anggakusuma et al, 2015;Song et al, 2017;Wang et al, 2017). In the present study, we investigated whether PEDV infection could upregulate CH25H expression in Vero cells.…”

Section: Pedv Infection Downregulates Ch25h Expression and Ch25h Is mentioning

confidence: 90%

“…The pCAGGS-CH25H-Flag was constructed and maintained in our laboratory. In addition, pCAGGS-CH25H-M-Flag lacking catalytic activity converted histidine residues 242 and 243 to glutamines by sitedirected mutagenesis and were constructed and conserved in our laboratory (Song et al, 2017). Vero cells or ST cells placed in 24-well plates were transfected with 1 μg of pCAGGS-CH25H-Flag, pCAGGS-CH25H-M-Flag, or pCAGGS using Lipmax as a transfection reagent (SUDGEN, Beijing, China), according to the manufacturer's manual.…”

Section: Plasmids and Small Interfering Rna (Sirna) Assaymentioning

confidence: 99%

“…1B). In addition, Vero cells were treated with 20,000 IU/ mL IFN-α (Song et al, 2017) and incubated for 4, 8, 12, 16, 24, and 36 h at 37°C. The CH25H and MX2 mRNA levels were measured by qRT-PCR.…”

Section: Pedv Infection Downregulates Ch25h Expression and Ch25h Is mentioning

confidence: 99%

“…The CH25H-M, which lacks catalytic activity owing to the conversion of histidine residues 242 and 243 to glutamines, and is incapable of producing 25HC, was created by site-directed mutagenesis and maintained in our laboratory (Song et al, 2017). To investigate whether the antiviral effect of CH25H was associated with enzymatic activity, Vero cells were transfected with plasmids containing pCAGGS-CH25H-Flag, pCAGGS-CH25H-M-Flag, and an empty vector, and then infected with the PEDV YZ strain (MOI of 0.01) containing 8 μg/mL trypsin at 24 h post-transfection.…”

Section: Overexpression Of Ch25h Inhibits Pedv Replicationmentioning

confidence: 99%

“…Cholesterol 25-hydroxylase (CH25H) encodes an ER-associated enzyme that catalyzes the oxidation of cholesterol to 25HC (Blanc et al, 2013;Hotter et al, 2013). Recent reports have revealed that CH25H inhibits many enveloped viruses, including vesicular stomatitis virus (VSV) (Liu et al, 2013), human immunodeficiency virus (HIV) (Moog et al, 1998), hepatitis C virus (HCV) (Anggakusuma et al, 2015), Ebola virus (EBOV) (Liu et al, 2013), porcine reproductive and respiratory syndrome virus (PRRSV) (Song et al, 2017), pseudorabies virus (PRV) and Zika virus (Li et al, 2017a), as well as some non-enveloped viruses, such as human rotavirus and human rhinovirus (Fessler, 2016). However, the antiviral effects and mechanisms of CH25H and 25HC on PEDV are still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Cholesterol 25-hydroxylase negatively regulates porcine intestinal coronavirus replication by the production of 25-hydroxycholesterol

Zhang

Song

Wang

et al. 2019

Veterinary Microbiology

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Cholesterol 25-hydroxylase Porcine epidemic diarrhea virus 25-hydroxycholesterol Porcine transmissible gastroenteritis virus A B S T R A C TCholesterol 25-hydroxylase (CH25H) has been shown lately to be a host restriction factor that encodes an enzyme, which catalyzes the oxidized form of cholesterol to 25-hydroxycholesterol (25HC). A series of studies have shown that 25HC activity in hosts plays a vital role in inhibiting viral infection. In this study, we explored the antiviral effect of CH25H and 25HC on porcine epidemic diarrhea virus (PEDV), which causes high mortality rates in newborn piglets with severe diarrhea, and considerable financial loss in the swine industry worldwide. Our results showed that PEDV infection downregulated the expression of CH25H in Vero cells. An overexpression and knockdown assay indicated that CH25H has significant antiviral action against PEDV, and a CH25H mutant (CH25H-M) that lacks hydroxylase activity also retains antiviral activity to a lesser extent. Furthermore, 25HC had a broad-spectrum antiviral effect against different PEDV strains by blocking viral entry. In addition, CH25H and 25HC inhibited the replication of porcine transmissible gastroenteritis virus (TGEV). Taken together, CH25H as a natural host restriction factor could inhibit PEDV and TGEV infection.

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Section: Pedv Infection Downregulates Ch25h Expression and Ch25h Is mentioning

confidence: 90%

Section: Plasmids and Small Interfering Rna (Sirna) Assaymentioning

confidence: 99%

Section: Pedv Infection Downregulates Ch25h Expression and Ch25h Is mentioning

confidence: 99%

Section: Overexpression Of Ch25h Inhibits Pedv Replicationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cholesterol 25-hydroxylase negatively regulates porcine intestinal coronavirus replication by the production of 25-hydroxycholesterol

Zhang

Song

Wang

et al. 2019

Veterinary Microbiology

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Cholesterol 25-hydroxylase suppresses rabies virus infection by inhibiting viral entry

et al. 2019

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Modulation of Antiviral Immunity and Therapeutic Efficacy by 25-Hydroxycholesterol in Chronically SIV-Infected, ART-Treated Rhesus Macaques

Zhao

et al. 2021

Virol. Sin.

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Cholesterol-25-hydroxylase (CH25H) and its enzymatic product 25-hydroxycholesterol (25HC) exert broadly antiviral activity including inhibiting HIV-1 infection. However, their antiviral immunity and therapeutic efficacy in a nonhuman primate model are unknown. Here, we report that the regimen of 25HC combined with antiretroviral therapy (ART), provides profound immunological modulation towards inhibiting viral replication in chronically SIV mac239 -infected rhesus macaques (RMs). Compared to the ART alone, this regimen more effectively controlled SIV replication, enhanced SIV-specific cellular immune responses, restored the ratio of CD4/CD8 cells, reversed the hyperactivation state of CD4 + T cells, and inhibited the secretion of proinflammatory cytokines by CD4 + and CD8 + T lymphocytes in chronically SIV-infected RMs. Furthermore, the in vivo safety and the preliminary pharmacokinetics of the 25HC compound were assessed in this RM model. Taken together, these assessments help explain the profound relationship between cholesterol metabolism, immune modulation, and antiviral activities by 25HC. These results provide insight for developing novel therapeutic drug candidates against HIV-1 infection and other related diseases. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00407-6.

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Cholesterol 25-hydroxylase is an interferon-inducible factor that protects against porcine reproductive and respiratory syndrome virus infection

Cited by 41 publications

References 34 publications

Cholesterol 25-hydroxylase negatively regulates porcine intestinal coronavirus replication by the production of 25-hydroxycholesterol

Cholesterol 25-hydroxylase negatively regulates porcine intestinal coronavirus replication by the production of 25-hydroxycholesterol

Cholesterol 25-hydroxylase suppresses rabies virus infection by inhibiting viral entry

Modulation of Antiviral Immunity and Therapeutic Efficacy by 25-Hydroxycholesterol in Chronically SIV-Infected, ART-Treated Rhesus Macaques

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