TY - JOUR
T1 - Heme oxygenase-1 modulates human respiratory syncytial virus replication and lung pathogenesis during infection
AU - Espinoza, Janyra A
AU - León, Miguel A.
AU - Céspedes, Pablo F.
AU - Gómez, Roberto S
AU - Canedo-Marroquín, Gisela
AU - Riquelme, Sebastián A.
AU - Salazar-Echegarai, Francisco J
AU - Blancou, Phillipe
AU - Simon, Thomas
AU - Anegon , Ignacio
AU - Lay, Margarita K
AU - González, Pablo A
AU - Riedel, Claudia
AU - Bueno, Susan M
AU - Kalergis, Alexis M.
N1 - Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85021111444&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1601414
DO - 10.4049/jimmunol.1601414
M3 - Article
C2 - 28566367
AN - SCOPUS:85021111444
SN - 0022-1767
VL - 199
SP - 212
EP - 223
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -
