African swine fever virus
African swine fever virus (ASFV) is a large, double-stranded DNA virus in the Asfarviridae family.[1] It is the causative agent of African swine fever (ASF). The virus causes a hemorrhagic fever with high mortality rates in domestic pigs; some isolates can cause death of animals as quickly as a week after infection. It persistently infects its natural hosts, warthogs, bushpigs, and soft ticks of the genus Ornithodoros, which likely act as a vector, with no disease signs.[2] It does not cause disease in humans.[3][4] ASFV is endemic to sub-Saharan Africa and exists in the wild through a cycle of infection between ticks and wild pigs, bushpigs, and warthogs. The disease was first described after European settlers brought pigs into areas endemic with ASFV, and as such, is an example of an emerging infectious disease.
ASFV replicates in the cytoplasm of infected cells.[1] It is the only virus with a double-stranded DNA genome known to be transmitted by arthropods.[5]
ASFV is a large (175–215 nm),[6] icosahedral, double-stranded DNA virus with a linear genome of 189 kilobases containing more than 180 genes.[7] The number of genes differs slightly among different isolates of the virus.[8] ASFV has similarities to the other large DNA viruses, e.g., poxvirus, iridovirus, and mimivirus. In common with other viral hemorrhagic fevers, the main target cells for replication are those of monocyte, macrophage lineage. Entry of the virus into the host cell is receptor-mediated, but the precise mechanism of endocytosis is presently unclear.[9]
The virus encodes enzymes required for replication and transcription of its genome, including elements of a base excision repair system, structural proteins, and many proteins that are not essential for replication in cells, but instead have roles in virus survival and transmission in its hosts. Virus replication takes place in perinuclear factory areas. It is a highly orchestrated process with at least four stages of transcription—immediate-early, early, intermediate, and late. The majority of replication and assembly occurs in discrete, perinuclear regions of the cell called virus factories, and finally progeny virions are transported to the plasma membrane along microtubules where they bud out or are propelled away along actinprojections to infect new cells. As the virus progresses through its lifecycle, most if not all of the host cell's organelles are modified, adapted, or in some cases destroyed.
Assembly of the icosahedral capsid occurs on modified membranes from the endoplasmic reticulum. Products from proteolytically processed polyproteins form the core shell between the internal membrane and the nucleoprotein core. An additional outer membrane is gained as particles bud from the plasma membrane. The virus encodes proteins that inhibit signalling pathways in infected macrophages and thus modulate transcriptional activation of immune response genes. In addition, the virus encodes proteins which inhibit apoptosis of infected cells to facilitate production of progeny virions. Viral membrane proteins with similarity to cellular adhesion proteins modulate interaction of virus-infected cells and extracellular virions with host components.[1]
Based on sequence variation in the C-terminal region of the B646L gene encoding the major capsid protein p72, 22 ASFV genotypes (I–XXIII) have been identified.[10] All ASFV p72 genotypes have been circulating in eastern and southern Africa. Genotype I has been circulating in Europe, South America, the Caribbean, and western Africa. Genotype VIII is confined to four East African countries.
