Nitric oxide is elicited and inhibits viral replication in pigs infected with porcine respiratory coronavirus but not porcine reproductive and respiratory syndrome virus

Jung, Kwonil; Gurnani, Ashita; Renukaradhya, Gourapura J.; Saif, Linda J.

There is little information on the role of nitric oxide ((•)NO) in innate immunity to respiratory coronavirus (CoV) infections. We examined (•)NO levels by Greiss assay in bronchoalveolar lavage (BAL) of pigs infected with either porcine respiratory coronavirus (PRCV) or porcine reproductive and respiratory syndrome virus (PRRSV), a member of Nidovirales, like CoV. The antiviral effects of (•)NO on these two viruses were tested in an in vitro system using a (•)NO donor, S-nitroso-N-acetylpenicillamine (SNAP). We detected a large increase in (•)NO levels in BAL fluids of PRCV-infected pigs, but not in PRRSV-infected pigs. Pulmonary epithelial cell necrosis induced by PRCV coincided with increased (•)NO. Moreover, (•)NO levels in cell culture medium of PRRSV-infected alveolar macrophages (AMs) did not differ from that of mock-infected AMs. Antiviral assays showed that (•)NO significantly inhibited PRCV replication in swine testicular (ST) cells, whereas PRRSV was not susceptible to (•)NO based on the conditions tested. Our study suggests that unlike PRRSV which induces apoptosis in AMs, respiratory CoVs such as PRCV that infect pulmonary epithelial cells and cause cytolysis, induce (•)NO production in the respiratory tract. Thus, (•)NO may play a role in innate immunity to respiratory CoV infections by inhibiting viral replication.