Abstract
Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in the degradation of heme, is induced in response to a wide range of stress conditions. HO-1 exerts antiviral activity against a broad range of viruses, including the Hepatitis C virus, the human immunodeficiency virus, and the dengue virus by inhibiting viral growth. It has been reported that HO-1 displays antiviral activity against the Zika virus (ZIKV) but the mechanisms of viral inhibition remain largely unknown. Using a ZIKV RNA replicon with the Green Fluorescent Protein (GFP) as a reporter protein, we were able to show that HO-1 expression resulted in the inhibition of viral RNA replication. Conversely, we observed a decrease in HO-1 expression in cells replicating the ZIKV RNA replicon. The study of human cells infected with ZIKV showed that the HO-1 expression level was significantly lower once viral replication was established, thereby limiting the antiviral effect of HO-1. Our work highlights the capacity of ZIKV to thwart the anti-replicative activity of HO-1 in human cells. Therefore, the modulation of HO-1 as a novel therapeutic strategy against ZIKV infection may display limited effect.
Highlights
IntroductionZika virus (ZIKV) is an emerging mosquito-borne flavivirus (family Flaviviridae), which has become a major medical problem worldwide
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus, which has become a major medical problem worldwide
We found that cobalt protoporphyrin (CoPP) treatment significantly reduced the percentage of Green Fluorescent Protein (GFP)-expressing cells at all tested doses and noted that CoPP was able to inhibit ZIKV replicon replication as efficiently as ribavirin
Summary
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus (family Flaviviridae), which has become a major medical problem worldwide. In 2007, the first documented outbreak of ZIKV occurred on Yap Island, affecting more than 70% of the population. ZIKV continued to spread in the South Pacific Islands and has largely emerged in the Americas since 2015 [1]. Phylogenetic analysis of viral sequences has identified two main virus lineages, African and Asian, the latter being the main cause of large, current epidemics with millions of cases of infection [2,3]. The human disease known as Zika fever is characterized by mild flu-like symptoms with fever, maculopapular rash, headache and sometimes conjunctivitis, arthralgia, and myalgia. Epidemiological studies from the recent epidemics have shown that infection due to ZIKV can
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