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Title: AFRICAN SWINE FEVER VIRUS MULTIGENE FAMILY 360 AND 530 GENES AFFECT HOST INTERFERON RESPONSE

Author
item Afonso, Claudio
item Piccone, Maria
item Zaffuto, Kristin
item Neilan, John
item Kutish, Gerald
item Lu, Zhiqiang
item Balinsky, Corey
item Gibb, Tammy
item Bean, Tanya
item Zsak, Laszlo
item Rock, Daniel

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2003
Publication Date: 2/1/2004
Citation: Afonso, C., Piccone, M.E., Zaffuto, K.M., Neilan, J.G., Kutish, G., Lu, Z., Balinsky, C.A., Gibb, T., Bean, T.R., Zsak, L., Rock, D.L. 2004. African swine fever virus multigene family 360 and 530 genes affect host interferon response.. Journal of Virology. (2004) 78 (4):1858-1864.

Interpretive Summary: Microarray technology is a reliable and powerful tool for gene expression profiling and for identification of the potential function of genes. In this paper we have used a cDNA 'chip hybridization to investigate the role of multigene family 360 and 530 genes (MG F360) of African swine fever virus (ASFV). By comparing the gene expression patterns of wild-type virus and MDF360/540 deletion mutant in infected cells, we proposed that MG360/540 genes either directly or indirectly suppress a type I IFN response. This is the first report using swine macrophages microarrays manufactured in PIADC, USDA.

Technical Abstract: African swine fever virus (ASFV) multigene family 360 and 530 (MGF360/530) genes affect viral growth in macrophage cell culture and virulence in pigs (L. Zsak, Z. Lu, T.G. Burrage, J.G. Neilan, G.F. Kutish, D.M. Moore, and D.L. Rock, J. Virol. 75:3066-3076, 2001). The mechanism by which these novel genes affect virus-host interactions is unknown. To define MGF360/530 gene function, we compared macrophage transcriptional responses following infection with parental ASFV (Pr4) and an MGF360/530 deletion mutant (Pr4delta35). A swine cDNA microarray containing 7,712 macrophage cDNA clones was used to compare the transcriptional profiles of swine macrophages infected with Pr4 and Pr4delta 35 at 3 and 6 h post infection (hpi). While 3 hpi most (7,564) of the genes had similar expression levels in cells infected with either virus, 38 genes had significantly increased (>2.0-fold, P< 0.05) mRNA levels in Pr4delta35-infected marophages. Similar up-regulation of these genes was observed at 6 hpi. Viral infection was required for this induced transcriptional response. Most Pr4delta35 up-regulated genes were part of a type I interferon (IFN) response or were genes that are normally induced by double-stranded RNA and/or viral infection. These included monocyte chemoattractant protein, transmembrane protein 3, tetraticopeptide repeat protein 1, a ubiquitin-like 17-kDa protein, ubiquitin-specific protease ISG43, an RNA helicase DEAD box protein, GT-binding MX protein, the cytokine IP-10, and the PKR activator PACT. Differential expression IFN early-response genes in Pr4delta 35 relative to Pr4 was confirmed by Northern blot analysis and real-time PCR. Analysis of IFN-alpha mRNA and secreted IFN-alpha in mock- and Pr4-infected macrophages but significant IFN-alpha levels at 24 hpi in Pr4delta 35-infected macrophages. The absence of IFN-alpha in Pr4-infected macrophages suggests that MGF360-530 genes either directly or indirectly suppress a type I IFN response. An inability to suppress host type I IFN responses may account for the growth defect of Pr4delta35 in macrophages and its attenuation in swine.