Abstract
Pseudorabies virus (PRV) infection brings about great economic losses to the swine industry worldwide, as there are currently no effective therapeutic agents or vaccines against this disease, and mutations in endemic wild virulent PRV strains result in immune failure of traditional vaccines. Heme oxygenase-1 (HO-1) catalyzes the conversion of heme into biliverdin (BV), iron and carbon monoxide (CO), all of which have been demonstrated to protect cells from various stressors. However, the role of HO-1 in PRV replication remains unknown. Thus, the present study aimed to investigate the effect of HO-1 on PRV replication and determine its underlying molecular mechanisms. The results demonstrated that induction of HO-1 via cobalt-protoporphyrin (CoPP) markedly suppressed PRV replication, while HO-1 specific small interfering RNA or inhibitor zinc-protoporphyrin partially reversed the inhibitory effect of CoPP on PRV replication. Furthermore, overexpression of HO-1 notably inhibited PRV replication, while knockdown of endogenous HO-1 expression promoted PRV replication. Mechanism analyses indicated that the HO-1 downstream metabolites, CO and BV/BR partially mediated the virus suppressive effect of HO-1. Taken together, the results of the present study suggest that HO-1 may be developed as a novel endogenous antiviral factor against PRV, and the HO-1/BV/CO system may constitute a unique antiviral protection network during PRV infection and interaction with host cells.
Highlights
Pseudorabies (PR), caused by the pseudorabies virus (PRV) and characterized by severe reproductive, respiratory and neurological disorders, is one of the most devastating infectious diseases in pigs that brings about great economic losses to the swine industry worldwide (Nauwynck et al, 2007; Freuling et al, 2017)
In order to understand the role of the stress-induced protective enzyme against Pseudorabies virus (PRV) infection, Heme oxygenase-1 (HO-1) expression was assessed in porcine kidney (PK)-15 and swine testis (ST) cells during PRV infection
Downregulated HO-1 expression was indicated to be dependent of PRV replication, as UV-inactivated PRV failed to affect HO-1 expression compared with the 0 hpi group (Figures 1A–D)
Summary
Pseudorabies (PR), caused by the pseudorabies virus (PRV) and characterized by severe reproductive, respiratory and neurological disorders, is one of the most devastating infectious diseases in pigs that brings about great economic losses to the swine industry worldwide (Nauwynck et al, 2007; Freuling et al, 2017). The virus has been reported to infect a variety of mammals, including ruminants, carnivores and rodents and cause ∼100% mortality, pigs are the only natural hosts for PRV in which latency is established (Mettenleiter, 1991). Previous studies have reported that HO-1 exerts a protective role against oxidative stress (Lee J.C. et al, 2014). HO-1 can suppress the replication of bovine viral diarrhea virus (BVDV) in vitro (Xiao et al, 2014). These previous studies emphasize the potential use of this cytoprotective enzyme as a virucidal agent. The molecular mechanism underlying the antiviral effect of HO-1 still remains largely unknown
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