Cytokine and nitric oxide production by mouse macrophages infected with Brazilian flaviviruses.

The Flaviviridae family, Flavivirus genus includes viruses that are transmitted to vertebrates by infected mosquitoes or ticks. The genus Flavivirus includes a variety of viruses that cause diseases such as acute febrile illness, encephalitis, and hemorrhagic fever. Flaviviruses primarily infect blood monocytes and tissue macrophages, which have been shown to be permissive, supporting viral replication and serving as virus reservoirs. On the other hand, these cells may have an important antiviral activity related to modulation by cytokine production and by the capacity of these cells to synthesize reactive free radicals such as nitric oxide (NO) which can have a microbicidal effect. The present study was performed in order to determine the production of cytokines interleukin-1beta (IL-1beta), tumor necrosis factor -alpha (TNF-alpha), transforming growth factor- beta (TGF-beta) and interferon -alpha (IFN-alpha) and NO by macrophages infected with one of four Brazilian flaviviruses, Bussuquara virus (BUSV), Yellow Fever virus (YFV), Rocio virus (ROCV) and Encephalitis Saint Louis virus (SLEV), and to verify the possible antiviral effect of NO during macrophage infection with ROCV. Moreover, we asked if the different viruses were able to regulate bacterial lipopolysaccharide (LPS) induced cytokine production. Our results showed that YFV and SLEV reduced the production of IL-1beta and TGF-beta by LPS-stimulated macrophages, while ROCV only diminished LPS-stimulated TGF-beta synthesis. On the other hand, BUSV more likely favored an enhancement of the LPS-induced production of IL-1beta by macrophages. Additionally, while most of the viruses stimulated the production of IFN-alpha, none of them altered the production of TNF-alpha by murine macrophages. Interestingly, all viruses induced synthesis of NO that was not correlated with antiviral activity for ROCV.