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Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo.
Antiviral Res. 2018 11; 159:55-62.AR

Abstract

Pseudorabies virus (PRV) is an important viral pathogen of pigs that causes huge losses in pig herds worldwide. Ivermectin is a specific inhibitor of importin-α/β-dependent nuclear transport and shows antiviral potential against several RNA viruses by blocking the nuclear localization of viral proteins. Since the replication of DNA viruses is in the nucleus, ivermectin may be functional against DNA virus infections if the DNA polymerase or other important viral proteins enter the nucleus via the importin-α/β-mediated pathway. Here, we determined whether ivermectin suppresses PRV replication in hamster kidney BHK-21 cells and investigated the effect of ivermectin on the subcellular localization of the PRV UL42 protein, the accessory subunit of PRV DNA polymerase. Also, an in vivo anti-PRV assay was conducted in mice. Our data demonstrate that ivermectin treatment inhibits PRV infection in cells in a dose-dependent manner. Treatment of PRV-infected cells with ivermectin significantly suppressed viral DNA synthesis and progeny virus production. Ivermectin disrupted the nuclear localization of UL42 by targeting the nuclear localization signal of the protein in transfected cells. Ivermectin treatment increased the survival rates of mice infected with PRV and relieved infection as indicated by lower clinical scores and fewer gross lesions in the brain. Together, our results suggest that ivermectin may be a therapeutic or preventative agent against PRV infection.

Authors+Show Affiliations

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. Electronic address: yzq8162@163.com.College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. Electronic address: wxlong@nwsuaf.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30266338

Citation

Lv, Changjie, et al. "Ivermectin Inhibits DNA Polymerase UL42 of Pseudorabies Virus Entrance Into the Nucleus and Proliferation of the Virus in Vitro and Vivo." Antiviral Research, vol. 159, 2018, pp. 55-62.
Lv C, Liu W, Wang B, et al. Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo. Antiviral Res. 2018;159:55-62.
Lv, C., Liu, W., Wang, B., Dang, R., Qiu, L., Ren, J., Yan, C., Yang, Z., & Wang, X. (2018). Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo. Antiviral Research, 159, 55-62. https://doi.org/10.1016/j.antiviral.2018.09.010
Lv C, et al. Ivermectin Inhibits DNA Polymerase UL42 of Pseudorabies Virus Entrance Into the Nucleus and Proliferation of the Virus in Vitro and Vivo. Antiviral Res. 2018;159:55-62. PubMed PMID: 30266338.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo. AU - Lv,Changjie, AU - Liu,Wenkai, AU - Wang,Bin, AU - Dang,Ruyi, AU - Qiu,Li, AU - Ren,Juan, AU - Yan,Chuanqi, AU - Yang,Zengqi, AU - Wang,Xinglong, Y1 - 2018/09/26/ PY - 2018/05/25/received PY - 2018/08/10/revised PY - 2018/09/24/accepted PY - 2018/9/30/pubmed PY - 2019/9/24/medline PY - 2018/9/30/entrez KW - Antiviral KW - DNA polymerase KW - Ivermectin KW - Nuclear import KW - Pseudorabies virus SP - 55 EP - 62 JF - Antiviral research JO - Antiviral Res VL - 159 N2 - Pseudorabies virus (PRV) is an important viral pathogen of pigs that causes huge losses in pig herds worldwide. Ivermectin is a specific inhibitor of importin-α/β-dependent nuclear transport and shows antiviral potential against several RNA viruses by blocking the nuclear localization of viral proteins. Since the replication of DNA viruses is in the nucleus, ivermectin may be functional against DNA virus infections if the DNA polymerase or other important viral proteins enter the nucleus via the importin-α/β-mediated pathway. Here, we determined whether ivermectin suppresses PRV replication in hamster kidney BHK-21 cells and investigated the effect of ivermectin on the subcellular localization of the PRV UL42 protein, the accessory subunit of PRV DNA polymerase. Also, an in vivo anti-PRV assay was conducted in mice. Our data demonstrate that ivermectin treatment inhibits PRV infection in cells in a dose-dependent manner. Treatment of PRV-infected cells with ivermectin significantly suppressed viral DNA synthesis and progeny virus production. Ivermectin disrupted the nuclear localization of UL42 by targeting the nuclear localization signal of the protein in transfected cells. Ivermectin treatment increased the survival rates of mice infected with PRV and relieved infection as indicated by lower clinical scores and fewer gross lesions in the brain. Together, our results suggest that ivermectin may be a therapeutic or preventative agent against PRV infection. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/30266338/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(18)30331-0 DB - PRIME DP - Unbound Medicine ER -