Early inhibition of nitric oxide production increases HSV-1 intranasal infection.
Here, we studied the role of nitric oxide (NO) production during the first steps of the respiratory infection of BALB/c mice with herpes simplex virus type 1 (HSV-1), strain F. Nitric oxide synthase II (NOS-II) mRNA and protein were detected by reverse transcription (RT)-PCR and dot blot, respectively in samples of lungs and turbinates early post-infection (p.i.). Immunohistochemical analysis revealed pulmonar macrophages and PMN expressing NOS-II in the lungs of infected animals. Animals intranasally treated with aminoguanidine (AG), a NOS inhibitor, during the first steps of infection, showed a dose-dependent increase in pneumonitis compared to controls. Viral titres in turbinates, lungs, and brains were higher in AG treated mice. Finally, histopathology studies revealed a stronger inflammation in eyes, and lungs of these animals. Taken together, these results suggest a role of NO in controlling primary HSV intranasal infection.
Gamba
Gisela
G
Laboratory of Immunochemistry, Department of Biological Chemistry, Faculty of Sciences, University of Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina.
Cavalieri
Hernan
H
Courreges
Maria C
MC
Massouh
Ernesto J
EJ
Benencia
Fabian
F
D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D006561:Herpes Simplex / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000302:isolation & purification / Q000502:physiology*; D015151:Immunoblotting; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011014:Pneumonia / Q000821:virology; D011024:Pneumonia, Viral / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014420:Turbinates / Q000473:pathology / Q000821:virology; D014779:Virus Replication
D006146:Guanidines; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine