PNKP knockdown by RNA interference inhibits herpes simplex virus-1 replication in astrocytes
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Herpes simplex virus-1 (HSV-1) is a major pathogen that causes various central nervous system (CNS) diseases, including herpes simplex encephalitis and meningitis. According to recent studies, PNKP significantly affects the proliferation of HSV-1 in astrocytes. Here, we used viral proliferation curves to confirm the significant inhibitory effects of PNKP on HSV-1 proliferation. PNKP downregulation was also confirmed by analyzing the transcription of viral genes. We found that PNKP downregulation affects the viral DNA copy number. This study preliminarily confirms that PNKP affects viral proliferation by affecting HSV-1 genome cyclization. These results also suggest that astrocytes play a specific role in preventing HSV-1 infection.
KeywordsHerpes simplex virus I (HSV-1) Replication PNKP Cyclization Primary culture Monkey
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- Guo Y, Audry M, Ciancanelli M, Alsina L, Azevedo J, Herman M, Anguiano E, Sancho-Shimizu V, Lorenzo L, Pauwels E, Philippe P B, Perez de Diego R, Cardon A, Vogt G, Picard C, Andrianirina Z Z, Rozenberg F, Lebon P, Plancoulaine S, Tardieu M, Valerie D, Jouanguy E, Chaussabel D, Geissmann F, Abel L, Casanova J L, and Zhang S Y. 2011. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J Exp Med, 208: 2083–2098.PubMedCentralPubMedCrossRefGoogle Scholar
- Jilani A, Ramotar D, Slack C, Ong C, Yang X M, Scherer S W, and Lasko D D. 1999. Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3′-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage. J Biol Chem, 274: 24176–24186.PubMedCrossRefGoogle Scholar
- Pasieka T J, Cilloniz C, Carter V S, Rosato P, Katze M G, and Leib D A. 2011. Functional genomics reveals an essential and specific role for Stat1 in protection of the central nervous system following herpes simplex virus corneal infection. J Virol, 85: 12972–12981.PubMedCentralPubMedCrossRefGoogle Scholar
- Reinert L S, Harder L, Holm C K, Iversen M B, Horan K A, Dagnaes-Hansen F, Ulhoi B P, Holm T H, Mogensen T H, Owens T, Nyengaard J R, Thomsen A R, and Paludan S R. 2012. TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice. J Clin Invest, 122: 1368–1376.PubMedCentralPubMedCrossRefGoogle Scholar
- Zolner A E, Abdou I, Ye R, Mani R S, Fanta M, Yu Y, Douglas P, Tahbaz N, Fang S, Dobbs T, Wang C, Morrice N, Hendzel M J, Weinfeld M, and Lees-Miller S P. 2011. Phosphorylation of polynucleotide kinase/phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage. Nucleic Acids Res, 39: 9224–9237.PubMedCentralPubMedCrossRefGoogle Scholar