Role of the DNA-Binding Protein pA104R in ASFV Genome Packaging and as a Novel Target for Vaccine and Drug Development

Abstract

The recent incursions of African swine fever (ASF), a severe, highly contagious, transboundary viral disease that affects members of the Suidae family, in Europe and China have had a catastrophic impact on trade and pig production, with serious implications for global food security. Despite efforts made over past decades, there is no vaccine or treatment available for preventing and controlling the ASF virus (ASFV) infection, and there is an urgent need to develop novel strategies. Genome condensation and packaging are essential processes in the life cycle of viruses. The involvement of viral DNA-binding proteins in the regulation of virulence genes, transcription, DNA replication, and repair make them significant targets. pA104R is a highly conserved HU/IHF-like DNA-packaging protein identified in the ASFV nucleoid that appears to be profoundly involved in the spatial organization and packaging of the ASFV genome. Here, we briefly review the components of the ASFV packaging machinery, the structure, function, and phylogeny of pA104R, and its potential as a target for vaccine and drug development.

Structure of African Swine Fever Virus and Associated Molecular Mechanisms Underlying Infection and Immunosuppression: A Review

“…However, pP1192R was thought to participate in genome segregation to facilitate the separation of newly-replicated DNA molecules. B354L and D345L are suggested to involve in processing DNA ends for strand exchange or single-strand annealing during recombination ( 63 ). p14, a late-stage non-structured protein expressed by ASFV 9GL is suppressed, leads to defective interference particles without a central nucleoid ( 64 ).…”

Identification of Linear B Cell Epitopes on CD2V Protein of African Swine Fever Virus by Monoclonal Antibodies

“…There are no commercial vaccines for ASF ( 31 , 32 ). Due to the lack of knowledge about the protective immunity of ASFV antigens and the understanding about the diversity of these protective antigens in nature, the progress of ASFV vaccine development and disease control has been hindered ( 2 , 33 – 35 ).…”

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

“…This protein plays a critical role in viral DNA replication and gene expression which is capable of wrapping DNA to stabilize it, and thus to prevent its denaturation under extreme environmental conditions. On the basis of knockdown experiments with small interfering RNAs, pA104R has been shown to be involved in viral transcription, DNA replication, and genome packaging 31,32 . The gene encoding protein pl0 shows a strong DNA‐binding activity with similar affinity for both double‐stranded and single‐stranded DNA 21 .…”