Piscine Vitamin D Receptors Vdra/Vdrb in the Absence of Vitamin D Are Utilized by Grass Carp Reovirus for Promoting Viral Replication

Song, Yun Jie; Zhang, Jie; Xiao, Jun; Feng, Hao; Xu, Zhi-Hong; Nie, Pin; Chang, Ming Xian

doi:10.1128/spectrum.01287-23

Cited by 5 publications

(4 citation statements)

References 59 publications

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“…Our previous study has shown that lowering cholesterol biosynthesis via lovastatin can block the production of VIBs mediated by grass carp vitamin D receptors Vdra/Vdrb ( 20 ). Since gcOSBP1 also promoted the numbers of VIBs, we next investigated the effect of cholesterol biosynthesis in the gcOSBP1-mediated promotion of GCRV replication.…”

Section: Resultsmentioning

confidence: 99%

“…We previously have demonstrated that cholesterol and vitamin D receptors Vdra/Vdrb are vital for the generation of VIBs, which are important functional sites for viral replication ( 20 ). Grass carp ARF1, a member of the Ras superfamily, is recruited to VIBs, and co-localized with the viral nonstructural protein NS80 and NS38 of GCRV.…”

Section: Discussionmentioning

confidence: 99%

“…To determine the potential interactions between gcOSBP1 and gcVAP-A/gcVAP-B, CIK cells were transfected with indicated plasmids for 48 h. All these samples were lysed in IP lysis buffer. Co-IP was performed according to the previously reported methods ( 19 , 20 ). Western blotting used the following antibodies: anti-FLAG (Sigma-Aldrich, 1:5000), anti-HA (Sigma-Aldrich, 1:5000), anti-GAPDH (Proteintech, 1:5000), anti-VP3 (1:1000), anti-VP5 (1:5000), anti-NS38 (1:5000), or anti-NS80 (1:5000) Abs.…”

Section: Methodsmentioning

confidence: 99%

“…At 24 hpi, the cells were used for RNA extraction. The qRT-PCR was performed according to our previously reported method ( 20 ). All primers used for qRT-PCR are listed in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

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Coordination of oxysterol binding protein 1 and VAP-A/B modulates the generation of cholesterol and viral inclusion bodies to promote grass carp reovirus replication

Li,

Zhang,

Chen

et al. 2024

Front. Immunol.

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Similar to other RNA viruses, grass carp reovirus, the causative agent of the hemorrhagic disease, replicates in cytoplasmic viral inclusion bodies (VIBs), orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of GCRV VIBs are poorly understood. This work demonstrates that GCRV manipulates grass carp oxysterol binding protein 1 (named as gcOSBP1) and vesicle-associated membrane protein–associated protein A/B (named as gcVAP-A/B), 3 components of cholesterol transport pathway, to generate VIBs. By siRNA-mediated knockdown, we demonstrate that gcOSBP1 is an essential host factor for GCRV replication. We reveal that the nonstructural proteins NS80 and NS38 of GCRV interact with gcOSBP1, and that the gcOSBP1 is recruited by NS38 and NS80 for promoting the generation of VIBs. gcOSBP1 increases the expression of gcVAP-A/B and promotes the accumulation of intracellular cholesterol. gcOSBP1 also interacts with gcVAP-A/B for forming gcOSBP1-gcVAP-A/B complexes, which contribute to enhance the accumulation of intracellular cholesterol and gcOSBP1-mediated generation of VIBs. Inhibiting cholesterol accumulation by lovastatin can completely abolish the effects of gcOSBP1 and/or gcVAP-A/B in promoting GCRV infection, suggesting that cholesterol accumulation is vital for gcOSBP1- and/or gcVAP-A/B-mediated GCRV replication. Thus, our results, which highlight that gcOSBP1 functions in the replication of GCRV via its interaction with essential viral proteins for forming VIBs and with host gcVAP-A/B, provide key molecular targets for obtaining anti-hemorrhagic disease grass carp via gene editing technology.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…At 24 hpi, the cells were used for RNA extraction. The qRT-PCR was performed according to our previously reported method ( 20 ). All primers used for qRT-PCR are listed in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

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