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Journal of Virology, April 2002, p. 3095-3104, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3095-3104.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Novel Swine Virulence Determinant in the Left Variable Region of the African Swine Fever Virus Genome

Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Greenport, New York 11944-0848

Received 15 October 2001/ Accepted 18 December 2001

Previously we have shown that the African swine fever virus (ASFV) NL gene deletion mutant E70NL is attenuated in pigs. Our recent observations that NL gene deletion mutants of two additional pathogenic ASFV isolates, Malawi Lil-20/1 and Pr4, remained highly virulent in swine (100% mortality) suggested that these isolates encoded an additional virulence determinant(s) that was absent from E70. To map this putative virulence determinant, in vivo marker rescue experiments were performed by inoculating swine with infection-transfection lysates containing E70 NL deletion mutant virus (E70NL) and cosmid DNA clones from the Malawi NL gene deletion mutant (MalNL). A cosmid clone representing the left-hand 38-kb region (map units 0.05 to 0.26) of the MalNL genome was capable of restoring full virulence to E70NL. Southern blot analysis of recovered virulent viruses confirmed that they were recombinant E70NL genomes containing a 23- to 28-kb DNA fragment of the Malawi genome. These recombinants exhibited an unaltered MalNL disease and virulence phenotype when inoculated into swine. Additional in vivo marker rescue experiments identified a 20-kb fragment, encoding members of multigene families (MGF) 360 and 530, as being capable of fully restoring virulence to E70NL. Comparative nucleotide sequence analysis of the left variable region of the E70NL and Malawi Lil-20/1 genomes identified an 8-kb deletion in the E70NL isolate which resulted in the deletion and/or truncation of three MGF 360 genes and four MGF 530 genes. A recombinant MalNL deletion mutant lacking three members of each MGF gene family was constructed and evaluated for virulence in swine. The mutant virus replicated normally in macrophage cell culture but was avirulent in swine. Together, these results indicate that a region within the left variable region of the ASFV genome containing the MGF 360 and 530 genes represents a previously unrecognized virulence determinant for domestic swine.

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