A CONSERVED AFRICAN SWINE FEVER VIRUS I-KAPPA-B HOMOLOG, 5EL, IS NONESSENTIAL FOR GROWTH IN-VITRO AND VIRULENCE IN DOMESTIC SWINE

An African swine fever virus (ASFV) gene with similarity to the cellul ar inhibitor of NF kappa B (I kappa B) was described in the pathogenic African isolate Malawi Lil-20/1 (ORF 5EL) and a cell-culture-adapted European virus, BA71V (ORF A238L). Recently, this gene was shown to be a functional I kappa B homolog capable of downregulating NF kappa B-r egulated gene expression. This observation suggests the gene may be of significance to aspects of ASFV pathogenesis and virulence in domesti c swine by interfering with a normal antiviral host response. Here we show, using nucleotide sequence analysis, that 5EL is highly conserved among Various African and European pathogenic field isolates and that in all cases its similarity to I kappa B genes is limited to the pres ence of four low complexity ankyrin repeats in the ASFV gene. The 5EL gene of Malawi Lil-20/1 encodes a 28-kDa protein which was expressed e arly in virus-infected macrophage cell cultures with maximum levels ob served at 3 to 5 hr postinfection. To study gene function, a Malawi Li l-20/1 5EL gene deletion mutant (Delta 5EL) was constructed. Growth ch aracteristics of Delta 5EL in porcine macrophage cell cultures were in distinguishable from those of the parental virus. And, Delta 5EL exhib ited an unaltered parental Malawi Lil-20/1 disease and virulence pheno type in domestic swine. Thus, although highly conserved among ASN isol ates, 5EL is nonessential for growth in porcine macrophages in vitro a nd for viral virulence in domestic swine. A possible role for this gen e in transmission of ASFV in nature, a setting which involves the cycl ing of ASFV between two highly adapted hosts, Ornithodoros ticks and w arthogs or bush pigs, in sub-Saharan Africa is discussed. (C) 1997 Aca demic Press.