Suppressive effect of PARP-1 inhibitor on JC virus replication in vitro

• Published in: Journal of medical virology Vol. 85; no. 1; pp. 132 - 137
• Main Authors: Nukuzuma, Souichi, Kameoka, Masanori, Sugiura, Shigeki, Nakamichi, Kazuo, Nukuzuma, Chiyoko, Takegami, Tsutomu
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2013; Wiley; Wiley Subscription Services, Inc
• Subjects: 3-aminobenzamide; Acquired immune deficiency syndrome; Antiviral Agents - metabolism; Antiviral drugs; Benzamides - metabolism; Biological and medical sciences; Cell Line; Cell Survival; Clinical outcomes; Drug therapy; Enzyme Inhibitors - metabolism; Fundamental and applied biological sciences. Psychology; Human viral diseases; Humans; IMR-32 cells; Infectious diseases; JC virus; JC Virus - drug effects; JC Virus - physiology; JCI cells; Medical sciences; Microbiology; Miscellaneous; Monoclonal antibodies; Neurons - virology; PARP-1; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Staining and Labeling; Tetrazolium Salts - metabolism; Thiazoles - metabolism; Viral diseases; Viral Load - drug effects; Virology; Virus Replication; Virus; JC virus; In vitro replication; 3-aminobenzamide; Polyomavirus; JCI cells; Papovaviridae; PARP-1; IMR-32 cells
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.23443

The incidence of progressive multifocal leukoencephalopathy (PML) has increased due to the AIDS pandemic, hematological malignancies, and immunosuppressive therapies. Recently, the number of cases of monoclonal antibody‐associated PML has increased in patients treated with immunomodulatory drugs such as natalizumab. However, no common consensus regarding PML therapy has been reached in clinical studies. In order to examine the suppression of JC virus (JCV) replication by 3‐aminobenzamide (3‐AB), a representative PARP‐1 inhibitor, a DNA replication assay was carried out using the neuroblastoma cell line IMR‐32 and IMR‐adapted JCV. The suppression of JCV propagation by 3‐AB was also examined using JCI cells, which are a carrier culture producing continuously high JCV titers. The results indicated that PARP‐1 inhibitors, such as 3‐aminobenzamide (3‐AB), suppress JCV replication and propagation significantly in vitro, as judged by DNA replication assay, hemagglutination, and real‐time PCR analysis. It has been also shown that 3‐AB reduced PARP‐1 activity in IMR‐32 cells. According to the results of the MTT assay, the enzyme activity of 3‐AB‐treated cells was slightly lower than that of DMSO‐treated cells. However, the significant suppression of JCV propagation is not related to the slight decrease in cell growth. To our knowledge, this is the first report that PARP‐1 inhibitor suppresses the replication of JCV significantly in neuroblastoma cell lines via the reduction of PARP‐1 activity. Thus, PARP‐1 inhibitors also may be a novel therapeutic drug for PML. J. Med. Virol. 85:132–137, 2012. © 2012 Wiley Periodicals, Inc.