Heme Oxygenase-1 Exerts Antiviral Activity against Hepatitis A Virus In Vitro

被引:9
作者
Kim, Dong-Hwi [1 ]
Ahn, Hee-Seop [1 ]
Go, Hyeon-Jeong [1 ]
Kim, Da-Yoon [1 ]
Kim, Jae-Hyeong [1 ]
Lee, Joong-Bok [1 ]
Park, Seung-Yong [1 ]
Song, Chang-Seon [1 ]
Lee, Sang-Won [1 ]
Choi, In-Soo [1 ]
机构
[1] Konkuk Univ, Coll Vet Med, Dept Infect Dis, 120 Neungdong Ro, Seoul 05029, South Korea
关键词
hepatitis A virus; heme oxygenase-1; hemin; antiviral therapeutics; MOLECULAR EPIDEMIOLOGY; UNITED-STATES; REPLICATION; INFECTION; INACTIVATION; INDUCTION; HIJACKING;
D O I
10.3390/pharmaceutics13081229
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Hepatitis A virus (HAV), the causative pathogen of hepatitis A, induces severe acute liver injuries in humans and is a serious public health concern worldwide. However, appropriate therapeutics have not yet been developed. The enzyme heme oxygenase-1 (HO-1) exerts antiviral activities in cells infected with several viruses including hepatitis B and C viruses. In this study, we demonstrated for the first time the suppression of virus replication by HO-1 in cells infected with HAV. Hemin (HO-1 inducer) induced HO-1 mRNA and protein expression, as expected, and below 50 mM, dose-dependently reduced the viral RNA and proteins in the HAV-infected cells without cytotoxicity. Additionally, HO-1 protein overexpression using a protein expression vector suppressed HAV replication. Although ZnPP-9, an HO-1 inhibitor, did not affect HAV replication, it significantly inhibited hemin-induced antiviral activity in HAV-infected cells. Additionally, FeCl3, CORM-3, biliverdin, and the HO-1 inducers andrographolide and CoPP inhibited HAV replication in the HAV-infected cells; andrographolide and CoPP exhibited a dose-dependent effect. In conclusion, these results suggest that HO-1 effectively suppresses HAV infection in vitro, and its enzymatic products appear to exert antiviral activity. We expect that these results could contribute to the development of a new antiviral drug for HAV.
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页数:12
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