Abstract
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.
Highlights
Hepatitis A, caused by infection with hepatitis A virus (HAV), presents clinical signs such as jaundice, fatigue, and abdominal pains
heme oxygenase-1 (HO-1) protein expression was grad(Figure 1C). These results showed that increased expression of HO-1 proteins could induce inhibition of HAVwith proliferation whileconcentrations increasing hemin ually increased increasing ofconcentration
We evaluated HO-1 as an antiviral protein against HAV infection
Summary
Hepatitis A, caused by infection with hepatitis A virus (HAV), presents clinical signs such as jaundice, fatigue, and abdominal pains. HAV, a positive sense single-stranded RNA virus with a 7.5 kb genome, is classified into the genus Hepatovirus of the family Picornaviridae [1]. HAV was originally classified as a non-enveloped virus; some studies revealed that it can exist in an enveloped form by hijacking cellular membranes [2,3]. Typical transmission of HAV occurs by direct contact with patients or ingestion of contaminated foods or water through the fecal–oral route [4,5,6]. HAV causes only acute hepatitis, not chronic hepatitis [7]. The degree of symptoms is more likely to be severe in older patients or patients with chronic liver diseases [8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
