Submitted to: Journal of General Virology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/9/2007
Publication Date: 9/1/2007
Citation: Zaffuto, K.M., Piccone, M.E., Burrage, T.G., Risatti, G.R., Borca, M.V., Holinka, L.G., Rock, D.L., Afonso, C.L. 2007. Classical Swine Fever Virus Inhibits Nitric Oxide Production in Infected Macrophages. Journal of General Virology. 88:3007-3012. Interpretive Summary: Classical swine fever virus (CSFV), is the causative agent of classical swine fever (CSF) a disease that causes outbreaks intermittently in Europe and other parts of world resulting in highly significant economic losses. CSF is a highly contagious and often fatal hemorrhagic disease of swine presenting as either an acute or chronic infection. Macrophages, a type of cell important in both the initiation and resolution phases of inflammation are the main cell types targeted by CSFV. Here, have identified changes in macrophage gene expression that occurs after CSFV infection and suggest that the virus is capable to manipulating the host to induce a favorable hypo-reactive state not previously observed for any RNA viruses. This discovery is significant because it associates CSFV infection with the control of nitric oxide production, thus providing an understanding on the mechanisms of disease.
Technical Abstract: Classical swine fever virus (CSFV)-macrophage interactions during infection were analyzed by examining macrophage transcriptional responses via microarray. Eleven genes had increased mRNA levels (>2.5 fold, p<0.05) in infected cell cultures including arginase-1, an inhibitor of nitric oxide production, phosphoinositide 3 kinase, chemokine receptor 4, and interleukin-1 beta. Genes with decreased expression (>2.5 fold, p<0.05) included angiotensin converting enzyme and osteopontin. Lower levels of nitric oxide and increased arginase activity were found in CSFV-infected macrophages. These changes in gene expression in macrophages suggest viral modulation of host expression to induce a favorable hypo-reactive state of differentiation not previously observed for RNA viruses.