Heme Oxygenase-1 Modulates Human Respiratory Syncytial Virus Replication and Lung Pathogenesis during Infection

Abstract

Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/β mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection.

Host heme oxygenase‐1: Friend or foe in tackling pathogens?

“…Furthermore, CoPP treatment upregulated expression IFN‐α/β in the lungs of hRSV‐infected mice. CoPP treatment reduced viral replication and decreased inflammatory cell infiltration and resolved the disease . These findings support a protective role of HMOX1 in hRSV infection.…”

The Cytoprotective Enzyme Heme Oxygenase-1 Suppresses Pseudorabies Virus Replication in vitro

“…Thus far, a number of studies have demonstrated the antiviral activity of HO-1. For example, induction or overexpression of HO-1 has been reported to inhibit infection of influenza (Hashiba et al, 2001), human immunodeficiency virus (HIV) (Devadas and Dhawan, 2006), hepatitis B virus (HBV) (Protzer et al, 2007), dengue virus (DENV) (Tseng et al, 2016), and human respiratory syncytial virus (RSV) (Espinoza et al, 2017). HO-1 has also exhibited antiviral properties within viruses effecting domestic animals.…”

Heme-Oxygenase-1 Expression Contributes to the Immunoregulation Induced by Fasciola hepatica and Promotes Infection

“…The role of HO-1 in infections by intracellular pathogens has been previously approached, demonstrating an upregulation of HO-1 mRNA and/or protein expression in response to viral (25), bacterial (23, 41–46), or protozoan parasitic (18, 19, 47) infections. Furthermore, overexpression or induction of HO-1 promotes persistence of other infectious agents, such as Leishmania chagasi and Plasmodium liver infection (18, 47).…”

“…For instance, HO-1 is able to promote Plasmodium liver infection (18), whereas it plays a favorable role in the host during cerebral malaria (19). On the other hand, HO-1 controls a variety of infections in mice, including Mycobacterium avium (20), Listeria monocytogenes (21), Plasmodium falciparum (22), Salmonella typhimurium (23), Toxoplasma gondii (24), and respiratory syncytial virus (25). …”