Summary auto-generated
African swine fever virus (ASFV) is a lethal pig disease with no available vaccine. Previous research showed that deletion of the NL gene from European ASFV isolate E70 substantially attenuated the virus in pigs. This study tested whether NL gene deletion would similarly reduce virulence in two African ASFV isolates: Malawi Lil-20/1 (Mal) and Pretoriuskop/96/4 (Pr4). Researchers constructed NL gene deletion mutants (Mal-∆NL and Pr4∆NL) and evaluated their virulence in domestic pigs. Unexpectedly, Mal-∆NL remained highly virulent with 100% mortality and disease similar to its revertant control. Pr4∆NL also retained high virulence with 86% mortality, though with delayed fever and death onset compared to parental virus. These results indicate that NL gene function is not absolutely required for ASFV virulence and that its role is strain-dependent. The findings suggest other yet-unidentified viral determinants contribute significantly to virulence in African isolates, implying that NL gene deletion alone is insufficient for developing live attenuated ASFV vaccines.
Key findings
- NL gene deletion mutants from African ASFV isolates (Mal and Pr4) remained highly virulent in domestic pigs, contrasting with near-complete attenuation observed with European E70 isolate NL deletion mutant
- The contribution of the NL gene to ASFV virulence is strain-dependent, ranging from complete attenuation to minimal effect across different isolates
- Other unidentified viral determinants must perform significant virulence functions in African ASFV isolates that can compensate for NL gene loss
- NL gene deletion alone is insufficient to engineer live attenuated ASFV vaccines suitable for use as protective vaccines
This summary was generated automatically from the article PDF and is not part of the original publication. Refer to the PDF for the authoritative text.
Abstract
Previously, we described a highly conserved nonessential African swine fever virus (ASFV) right variable region gene, NL. Deletion of NL from the European pathogenic isolate E70 resulted in almost complete attenuation of the virus in domestic swine. To study gene function further, NL gene deletion mutants were constructed from two pathogenic African ASFV isolates, Malawi Lil-20/1 (Mal) and Pretoriuskop/96/4 (Pr4). Unexpectedly, both Mal (Mal-deltaNL) and PR4 (Pr4deltaNL) null mutants remained highly virulent when inoculated in swine. Mal-deltaNL exhibited a disease and virulence phenotype indistinguishable from its revertant, Mal-NLR, which caused 100% mortality. Mortality among Pr4deltaNL-infected animals was also high; however, a significant delay in onset of fever and viraemia and in time to death was observed. These data indicate that NL gene function is not required for ASFV virulence and that other yet-to-be identified viral determinants perform significant virulence functions in these African field isolates.