Inhibition of nitric oxide induction from avian macrophage cell lines by influenza virus.

The virulent avian influenza virus A/Ty/Ont/7732/66 (H5N9) (Ty/Ont) causes a rapid destruction of lymphoid cells in infected birds. Avian macrophage cell lines, HD11 and MQ-NCSU, support productive replication of Ty/Ont and other influenza viruses. Therefore, the ability of these cell lines to produce nitric oxide (NO), a potentially cytotoxic mediator, in response to infection with Ty/Ont was examined. Although treatment with bacterial lipopolysaccharides (LPS) resulted in high NO levels, infection of macrophages with Ty/Ont resulted in NO levels lower than NO levels in untreated cells. Furthermore, Ty/Ont was able to inhibit the positive response to LPS in cultures simultaneously treated with LPS and virus. However, inactivated influenza virus did not exhibit this inhibitory effect. Different strains of influenza virus varied in their ability to inhibit NO production by the macrophages; this may be related to the level of virus replication in these cells. These data suggest that the ability of the avian macrophage to activate the NO synthesis pathway is seriously impaired by infection with virulent influenza viruses such as Ty/Ont.