Inhibition of endocytosis of porcine reproductive and respiratory syndrome virus by rottlerin and its potential prophylactic administration in piglets

• Published in: Antiviral research 2021-11, Vol.195, p.105191-105191, Article 105191
• Main Authors: Kang, Yeong-Lim, Oh, Changin, Ahn, So-Hyun, Choi, Jong-Chul, Choi, Hwi-Yeon, Lee, Sang-Won, Choi, In-Soo, Song, Chang-Seon, Lee, Joong-Bok, Park, Seung-Yong
• Format: Article
• Language: English
• Subjects: Acetophenones - pharmacology; Animals; Antiviral Agents - pharmacology; Antivirals; Benzopyrans - pharmacology; Cell Line; Endocytosis - drug effects; Liposome; Lung Diseases, Interstitial - prevention & control; Porcine Reproductive and Respiratory Syndrome - drug therapy; Porcine Reproductive and Respiratory Syndrome - pathology; Porcine respiratory and reproductive syndrome virus - drug effects; Protein kinase C; PRRSV; Rottlerin; Swine; Viral Load - drug effects; Virus Internalization - drug effects; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2021.105191

Owing to several limitations of porcine reproductive and respiratory syndrome virus (PRRSV) control procedures, the importance of antiviral agents is increasing; however, limited studies have been done on the development of anti-PRRSV agents. Herein, we explored the antiviral effect and mechanism of rottlerin against PRRSV. We demonstrated that treatment of rottlerin at an early stage of PRRSV infection significantly inhibited the viral replication. PRRSV infection induced protein kinase C-δ phosphorylation, which was specifically downregulated by rottlerin. The treatment of rottlerin led to disrupting the PRRSV entry pathway by blocking endocytosis of the virions. Further, to evaluate the anti-PRRSV effect of the rottlerin in vivo, we administrated rottlerin loaded liposome to pigs infected with PRRSV LMY or FL12 strain. The treatment of rottlerin-liposome reduced the blood viral load, interstitial pneumonia and clinical scores compared to untreated pigs. These results provide an evidence of anti-PRRSV effect of rottlerin in vitro via inhibiting PRRSV internalization and in vivo, all of which strongly suggest the applicability of rottlerin as a potential PRRSV prophylactic treatment. •Rottlerin inhibited PRRSV infection at an early stage in dose-dependent manner.•Rottlerin blocked the endocytosis of PRRSV.•Treatment of rottlerin loaded liposome reduced viremia, microscopic lung lesions and clinical scores in PRRSV-infected pigs.