4-Phenyl-butyric Acid Inhibits Japanese Encephalitis Virus Replication via Inhibiting Endoplasmic Reticulum Stress Response

Wang, Shuangshuang; Yang, Keli; Li, Chang; Liu, Wei; Gao, Ting; Yuan, Fangyan; Guo, Rui; Liu, Zewen; Tan, Yiqing; Hu, Xianwang; Tian, Yao; Zhou, Danna

doi:10.3390/v15020534

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…Tissue samples collected from the gastrointestinal tract were fixed in 4 % paraformaldehyde. Histopathology analysis was performed following our previous procedures [15]. For pathological examination, the paraffin-embedded tissues were cut into 2-3 µm-thick sections for haematoxylin and eosin (H and E) staining.…”

Section: Histopathology and Ihc Analysismentioning

confidence: 99%

Elucidating the biological characteristics and pathogenicity of the highly virulent G2a porcine epidemic diarrhea virus

Li,

Wu,

Song

et al. 2024

Journal of General Virology

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Since the large-scale outbreak of porcine epidemic diarrhoea (PED) in 2010, caused by the genotype 2 (G2) variant of the porcine epidemic diarrhoea virus (PEDV), pig farms in China, even those vaccinated with the G2b vaccine, have experienced infections from the G2a variant, leading to significant economic losses. This study successfully isolated the G2a strain DY2020 from positive small intestine contents (SICs) by blind passage on Vero cells for four generations. The SICs were taken from Daye, Hubei Province, China. The biological characteristics were identified by indirect immunofluorescence assay (IFA) and transmission electron microscopy (TEM). The growth kinetics of the strain on Vero cells were detected by TCID50, and the virus titre could reach 107.35 TCID50 ml−1 (SD: 5.07×106). The pathogenicity towards colostrum-deprived piglets was conducted by assessing faecal viral shedding, morphometric analysis of intestinal lesions, and immunohistochemical staining. The results showed that DY2020 was highly virulent to colostrum-deprived piglets, with severe watery diarrhoea and other clinical symptoms appeared at 6 h post-infection (h p.i.), and all died within 30 h. Pathological tissue examination results showed that the lesions mainly occurred in the intestines of piglets, causing pathological changes such as shortening of intestinal villi. In summary, the discovery of the G2a strain DY2020 in this study is of great significance for understanding Hubei PEDV and provides an important theoretical basis for the development of new efficient PEDV vaccines.

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Section: Histopathology and Ihc Analysismentioning

confidence: 99%

Elucidating the biological characteristics and pathogenicity of the highly virulent G2a porcine epidemic diarrhea virus

Li,

Wu,

Song

et al. 2024

Journal of General Virology

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Screening a neurotransmitter-receptor-related inhibitor library identifies clomipramine HCl as a potential antiviral compound against Japanese encephalitis virus

Liu,

Wang,

et al. 2024

Infectious Medicine

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Endoplasmic reticulum stress triggers unfolded protein response as an antiviral strategy of teleost erythrocytes

Salvador-Mira,

Sanchez-Cordoba,

Solivella

et al. 2024

Front. Immunol.

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IntroductionFish nucleated red blood cells (RBCs), also known as erythrocytes, play a crucial role in maintaining immune system balance by modulating protein expression in response to various stimuli, including viral attack. This study explores the intriguing behavior of rainbow trout RBCs when faced with the viral hemorrhagic septicemia virus (VHSV), focusing on the endoplasmic reticulum (ER) stress and the unfolded protein response (UPR).MethodsRainbow trout RBCs were Ficoll-purified and exposed to ultraviolet (UV)-inactivated VHSV or live VHSV at different multiplicities of infection (MOIs). Using cryo-soft X-ray tomography (cryo-SXT), we uncovered structural and cellular modifications in RBCs exposed to UV-inactivated VHSV. Moreover, RBCs were treated with 4-phenylbutyric acid (4-PBA), an ER stress inhibitor, to investigate its effect on viral replication. Quantitative real-time PCR was also used to analyze the expression of genes related to the UPR and other related cellular pathways.Results and discussionBeyond their antiviral response, RBCs undergo notable intracellular changes to combat the virus. Cryo-SXT highlighted a significant increase in the ER volume. This increase is associated with ER stress and the activation of the UPR pathway. Interestingly, VHSV replication levels augmented in RBCs under ER-stress inhibition by 4-PBA treatment, suggesting that rainbow trout RBCs tune up ER stress to control viral replication. Therefore, our findings suggested the induction of ER stress and subsequent activation UPR signaling in the antiviral response of RBCs to VHSV. The results open a new line of investigation to uncover additional mechanisms that may become novel cellular targets for the development of RBC-targeted antiviral strategies.

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4-Phenyl-butyric Acid Inhibits Japanese Encephalitis Virus Replication via Inhibiting Endoplasmic Reticulum Stress Response

Cited by 3 publications

References 48 publications

Elucidating the biological characteristics and pathogenicity of the highly virulent G2a porcine epidemic diarrhea virus

Elucidating the biological characteristics and pathogenicity of the highly virulent G2a porcine epidemic diarrhea virus

Screening a neurotransmitter-receptor-related inhibitor library identifies clomipramine HCl as a potential antiviral compound against Japanese encephalitis virus

Endoplasmic reticulum stress triggers unfolded protein response as an antiviral strategy of teleost erythrocytes

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