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. J. Med. Virol. 73:313–322, 2004. © 2004 Wiley‐Liss, Inc.