Human heme oxygenase 1 is a potential host cell factor against dengue virus replication
Citations Over TimeTop 10% of 2016 papers
Abstract
Dengue virus (DENV) infection and replication induces oxidative stress, which further contributes to the progression and pathogenesis of the DENV infection. Modulation of host antioxidant molecules may be a useful strategy for interfering with DENV replication. In this study, we showed that induction or exogenous overexpression of heme oxygenase-1 (HO-1), an antioxidant enzyme, effectively inhibited DENV replication in DENV-infected Huh-7 cells. This antiviral effect of HO-1 was attenuated by its inhibitor tin protoporphyrin (SnPP), suggesting that HO-1 was an important cellular factor against DENV replication. Biliverdin but not carbon monoxide and ferrous ions, which are products of the HO-1 on heme, mediated the HO-1-induced anti-DENV effect by non-competitively inhibiting DENV protease, with an inhibition constant (Ki) of 8.55 ± 0.38 μM. Moreover, HO-1 induction or its exogenous overexpression, rescued DENV-suppressed antiviral interferon response. Moreover, we showed that HO-1 induction by cobalt protoporphyrin (CoPP) and andrographolide, a natural product, as evidenced by a significant delay in the onset of disease and mortality, and virus load in the infected mice's brains. These findings clearly revealed that a drug or therapy that induced the HO-1 signal pathway was a promising strategy for treating DENV infection.
Related Papers
- → The heme-heme oxygenase system: a molecular switch in wound healing(2003)132 cited
- → Heme oxygenase-2 (HO-2) binds and buffers labile ferric heme in human embryonic kidney cells(2021)23 cited
- → Molecular basis for heme‐dependent induction of heme oxygenase in primary cultures of chick embryo hepatocytes(1993)45 cited
- → Heme oxygenase—regulation of and physiological implication in heme catabolism(1994)26 cited
- → Mechanism of induction of heme oxygenase by metalloporphyrins in primary chick embryo liver cells: Evidence against a stress-mediated response(1997)19 cited