Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen that causes significant economic losses in the global swine industry. Commercial vaccines provide limited protection against this virus, and no highly effective therapeutic drugs are yet available. In this study, we first screened a library of 386 natural products and found that xanthohumol (Xn), a prenylated flavonoid found in hops, displayed high anti-PRRSV activity by inhibiting PRRSV adsorption onto and internalization into cells. Transcriptome sequencing revealed that Xn treatment stimulates genes associated with the antioxidant response in the nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. Xn causes increased expression of Nrf2, HMOX1, GCLC, GCLM, and NQO1 in Marc-145 cells. The action of Xn against PRRSV proliferation depends on Nrf2 in Marc-145 cells and porcine alveolar macrophages (PAMs). This finding suggests that Xn significantly inhibits PRRSV proliferation and decreases viral-induced oxidative stress by activating the Nrf2–HMOX1 pathway. This information should be helpful for developing a novel prophylactic and therapeutic strategy against PRRSV infection.
Highlights
Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically detrimental swine diseases worldwide
Xanthohumol inhibits Porcine reproductive and respiratory syndrome virus (PRRSV) infection To begin to determine the mechanism of Xn inhibition of PRRSV, Marc-145 cells were treated with Xn before, during, and after PRRSV infection (Figure 3A)
Xanthohumol upregulates the nuclear factor-erythroid 2-related factor 2 (Nrf2)–HMOX1 antioxidative axis to inhibit PRRSV proliferation in porcine alveolar macrophages (PAMs) Given that PAMs are natural target cells in pigs, we identified the role of Xn in PRRSV-infected PAMs
Summary
Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically detrimental swine diseases worldwide. Infection is characterized by reproductive failure and preterm birth in sows as well as dyspnoea of piglets and fattening pigs [1, 2]. Modified live virus (MLV) vaccines protect against homologous strains [6], The interaction between PRRSV and pigs has been well studied. Several host antiviral factors, such as the interferon-stimulated genes (ISGs) viperin [8], myxovirus resistance 2 (Mx2) [9], 2′,5′-oligoadenylate synthetase 1 (OAS1) [10], interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) [11], and CH25H [12, 13], have been reported to have antiviral activity against PRRSV infection.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
