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

Janyra A Espinoza (1) , Miguel A León (1) , Pablo F Céspedes (1) , Roberto S. Gomez (1) , Gisela Canedo-Marroquín (1) , Sebastián A Riquelme (1) , Francisco J Salazar-Echegarai (1) , Phillipe Blancou (2) , Thomas Simon (2) , Ignacio Anegon (2) , Margarita K Lay (3) , Pablo A Gonzalez (1) , Claudia A Riedel (4) , Susan M Bueno (1) , Alexis M Kalergis (2, 1, 5)

1 Facultad de Ciencias Biologicas - Departamento de Microbiologıa y Genetica Molecular [Santiago, Chile]
2 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
3 Facultad de Ciencias del Mar y Recursos Biologicos - Departamento de Biotecnologıa [Antofagasta, Chile]
4 Facultad de Ciencias Biologicas y Facultad de Medicina - Departamento de Ciencias Biologicas [Santiago, Chile]
5 Facultad de Medicina - Departamento de Endocrinología [Santiago, Chile]

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 susceptiblepopulation.Inthisstudy,weexaminedtheeffectsofinducingtheactivityofthehostenzymehemeoxygenase-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-a/b 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.

Domaines: Médecine humaine et pathologie

Janyra A Espinoza, Miguel A León, Pablo F Céspedes, Roberto S. Gomez, Gisela Canedo-Marroquín, et al.. Heme Oxygenase-1 Modulates Human Respiratory Syncytial Virus Replication and Lung Pathogenesis during Infection. Journal of Immunology, 2017, 199 (1), pp.212-223. ⟨10.4049/jimmunol.1601414⟩. ⟨inserm-02154790⟩