Evaluation in Swine of a Recombinant Georgia 2010 African Swine Fever Virus Lacking the I8L Gene

Abstract

African swine fever virus (ASFV) is the causative agent of African swine fever, a disease currently causing significant economic losses in Europe and Asia. Specifically, the highly virulent ASFV strain Georgia 2010 (ASFV-G) is producing disease outbreaks in this large geographical region. The ASFV genome encodes for over 150 genes, most of which are still not experimentally characterized. I8L is a highly conserved gene that has not been studied beyond its initial description as a virus ORF. Transcriptional analysis of swine macrophages infected with ASFV-G demonstrated that the I8L gene is transcribed early during the virus replication cycle. To assess the importance of I8L during ASFV-G replication in vitro and in vivo, as well as its role in virus virulence in domestic swine, we developed a recombinant virus lacking the I8L gene (ASFV-G-ΔI8L). Replication of ASFV-G-ΔI8L was similar to parental ASFV-G replication in primary swine macrophage cultures, suggesting that the I8L gene is not essential for ASFV-G replication in vitro. Similarly, replication of ASFV-G-ΔI8L in swine intramuscularly inoculated with 102 HAD50 displayed replication kinetics similar to ASFV-G. In addition, animals inoculated with ASFV-G-ΔI8L presented with a clinical disease indistinguishable from that induced by the same dose of the virulent parental ASFV-G isolate. We conclude that deletion of the I8L gene from ASFV-G does not affect virus replication in vitro or in vivo, nor changes the disease outcome in swine.

African Swine Fever Virus and Host Response: Transcriptome Profiling of the Georgia 2007/1 Strain and Porcine Macrophages

“…Interestingly, loss of MGF 100 members was observed during the process of adapting a virulent Georgia strain to grow in cultured cell lines ( 60 ). Deletion of MGF 100-1R, from a virulent genotype II Chinese strain ( 73 ), or of l8L from Georgia 2010 was shown not to reduce virulence of the virus in pigs or reduce virus replication in porcine macrophages ( 74 ). However, simultaneous deletion of genes l7L, l8L, l9L, l10L, and l11L from a Chinese virulent isolate reduced virulence, and surviving pigs were protected against challenge ( 59 ).…”

Evaluation of an ASFV RNA Helicase Gene A859L for Virus Replication and Swine Virulence

“…A small number of ASFV genes have been successfully deleted from the ASFV genome (e.g., TK, NL, CD2, MGF360-16R and 1L, MGF110-1L, L83L, C962R, X69R, I8L) [9][10][11][12][13][14][15][16][17][18], while another small number of genes have been shown essential for virus replication (e.g., EP152R, p30, p54, p72) [19][20][21][22]. These studies demonstrate that deleting specific genes by genetic manipulation of the virus genome is a powerful approach to study the function of a particular gene or group of genes during infection.…”

African Swine Fever Virus and host response - transcriptome profiling of the Georgia 2007/1 strain and porcine macrophages

“…Interestingly, loss of MGF 100 members was observed during the process of adapting a virulent Georgia strain to grow in cultured cell lines (60). Deletion of MGF 100-1R, from a virulent genotype II Chinese strain (72) or of l8L from Georgia 2010 was shown not to reduce virulence of the virus in pigs or reduce virus replication in porcine macrophages (73). However, simultaneous deletion of genes l7L, l8L, l9L, l10L and l11L from a Chinese virulent isolate reduced virulence and surviving pigs were protected against challenge (59).…”