The structural basis of African swine fever virus core shell protein p15 binding to DNA

Abstract

African swine fever (ASF) is an acute, hemorrhagic, and highly contagious disease caused by African swine fever virus (ASFV). The mortality rate of acute infection up to 100% have posed an unprecedented challenge of the swine industry. Currently no commercial antiviral drug is available for the control and treatment of ASFV. The structural resolution of ASFV virions reveals the details of ASFV morphogenesis, providing a new perspective for the research and promotion of the development of ASFV vaccines. Although the architecture of ASFV have been solved via cryo‐EM, the structural details of four of the five viral layers remain unclear (except the outer capsid). In this study, we resolved the crystal structure of the ASFV core shell protein p15. The secondary structural elements of a protomer include four α‐helix structures and six antiparallel β‐strands. Further analysis revealed that ASFV p15 forms disulfide‐linked trimers between the Cys9 from one protomer and Cys30 from other protomer. Additionally, the nucleic acid‐binding property was characterized by electrophoretic mobility shift assay. Two critical amino acid Lys10 and Lys39 have been identified which is essential to the nucleic acid‐binding affinity of ASFV p15. Together, these findings may provide new insight into antiviral drug development.

Proteome Analysis of Swine Macrophages after Infection with Two Genotype II African Swine Fever Isolates of Different Pathogenicity

“…It was interesting to observe N-truncation variants arising from the B646L gene, encoding the p72 capsid protein which is essential for virion assembly. There are now structures available of p72 alone [ 71 ] ( Figure 3 B), as well as in the context of the ASFV capsid structure [ 72 , 73 ] enabling a structure-based analysis of N-truncated p72 proteins generated by intra-ORF TSS’s like nORF_105178. This nORF began 127 residues after the p72 start codon, which, according to the structure from Liu et al, 2019 would omit the first 5 β-strands.…”

Clinical sequencing uncovers the genomic characteristics and mutation spectrum of the 2018 African swine fever virus in Guangdong, China

“…African swine fever (ASF) is a highly contagious viral disease in swine which exhibit a high mortality rate approaching 100% (1)(2)(3). ASF virus (ASFV), the causative agent of ASF, belongs to the order Asfuvirales, family Asfarviridae, and genus Asfivirus (4). ASFV was first introduced in northeast China in August 2018.…”

Structures and Functional Diversities of ASFV Proteins

“…ASFV p15 forms disulfide-linked trimers between the Cys9 and Cys30 from two different protomers [1]. The protomer secondary structural elements include four α-helix structures and six antiparallel β-strands.…”

“…Additionally, two critical residues Lys10 and Lys39 are essential to the nucleic acid-binding affinity of ASFV p15. The disulfide bonds are important for the trimerization of ASFV p15, demonstrating a stronger binding affinity to ssDNA than to dsDNA [1].…”

“…African swine fever (ASF) is an acute hemorrhagic viral disease caused by the African swine fever virus (ASFV), affecting wild boar and domestic pigs. ASFV is the only member of the Asfarviridae family which is an enveloped icosahedral deoxyvirus and shares similar structural, genomic, and replicative characteristics with other nucleocytoplasmic large DNA viruses (NCLDVs) [1]. A great deal of large DNA viruses have been found in the past two decades, and few of them have caused as great an economic impact to society as ASFV [2].…”