Type Species

African swine fever virus

(ASFV)

Virion Properties

Morphology

Virions consist of a nucleoprotein core structure, 70-100 nm in diameter, surrounded by internal lipid layers and an icosahedral capsid, 170 to 190 nm in diameter, and an external lipid-containing envelope. The capsid exhibits icosahedral symmetry (T = 189-217) corresponding to 1,892-2,172 capsomers (each capsomer is 13 nm in diameter and appears as a hexagonal prism with a central hole; intercapsomeric distance is 7.4-8.1 nm). Extracellular enveloped virions have a diameter of 175 to 215 nm (Fig. 1).

Physicochemical and Physical Properties

Virion buoyant density is 1.095 g/cm³ in Percoll, 1.19-1.24 g/cm³ in CsCl; S_20w is about 3,500S. Virions are sensitive to ether, chloroform and deoxycholate and are inactivated at 60°C within 30 minutes, but survive for years at 20°C or 4°C. Infectivity is stable over a wide pH range. Some infectious virus may survive treatment at pH4 or pH13. Infectivity is destroyed by some disinfectants (1% formaldehyde in 6 days, 2% NaOH in 1 day); paraphenylphenolic disinfectants are very effective. Virus is sensitive to irradiation.

Nucleic Acid

The genome consists of a single molecule of linear, covalently close-ended, dsDNA 170 to 190 kbp in size (varying among isolates). The end sequences are present as two flip-flop forms that are inverted and complementary with respect to each other, adjacent to both termini are identical tandem repeat arrays about 2.1 kbp long. The complete nucleotide sequence of the tissue culture adapted Ba71V isolate has been published as well as about 90 kbp from the virulent Malawi LIL20/1 isolate and 15 kbp from the LIS 57 isolate. The genome encodes about 150 ORFs.

Proteins

Virions contain more than 50 proteins including a number of enzymes and factors needed for early mRNA transcription and processing. Enzymes packaged include RNA polymerase, poly A polymerase, guanyl transferase, protein kinase. Major virion structural proteins characterized include p72, p30, the products of a Mr 220 10³ protein which is cleaved to give four structural proteins; p150, p37, p14 and p34, the products of a Mr 62 10³ protein which is cleaved to give two structural proteins p35 and p15. Two DNA binding proteins, p10 and p14.5 and seven proteins which contain putative transmembrane regions (p12, p17, p22, p54 or j13L, j18L, j5R and EP402R) are present in virions. Other predicted proteins encoded by the virus include enzymes involved in nucleotide metabolism (ribonucleotide reductase, thymidine kinase, thymidylate kinase, deoxyuridine triphosphatase), DNA replication and repair or transcription (DNA polymerase, DNA ligase, topoisomerase II, guanyl transferase, three members of DNA helicase superfamily II, 8-hydroxy GTPase, AP endonuclease). Two enzymes involved in post-translational protein modification (a ubiquitin conjugating enzyme and a serine/threonine protein kinase) and an enzyme involved in synthesis of isoprenoid compounds (trans-prenyltransferase) are encoded by the virus. Five different multigene families are found in genome regions close to the termini. Large length variations between genomes of different isolates are due to gain or loss of members of these families. Proteins which may modulate the host response to virus infection include those similar to the T cell surface protein CD2, IkB, the apoptosis inhibitors Bcl2 and IAP and one protein that is similar to a Herpes simplex virus encoded neurovirulence factor (ICP34.5), a myeloid differentiation antigen (Myd116), and the gadd34 protein. In addition, 26 proteins with predicted transmembrane domains are encoded and these may include proteins which modify host cell function in addition to proteins involved in virion morphogenesis.

Lipids

Enveloped virions contain lipids including glycolipids.

Carbohydrates

One virion protein is glycosylated (EP402R) and glycolipids are also incorporated into virions. The virus encodes several predicted transmembrane proteins that contain putative N-linked glycosilation sites.

Genome Organization and Replication

The 150 major ORFs are closely spaced (intergenic distances are generally less than 200 bp) and read from both DNA strands. A few intergenic regions contain short tandem repeat arrays (Fig. 2).

The virus replicates mainly in swine macrophages in vivo and in vitro although several isolates have been adapted to replicate in tissue culture cell lines. Virus enters cells by receptor mediated endocytosis and early mRNA synthesis begins in the cytoplasm immediately following entry using enzymes and factors packaged in the virus core. Virus DNA replication and assembly takes place in perinuclear factory areas. DNA replication peaks about 8 hours post-infection; head-to-head concatameric forms of DNA, which may be replicative DNA intermediates are found in cells at this time. DNA replication may proceed by a self-priming mechanism. The cell nucleus is required for productive infection.

Virus transcripts are 3-polyadenylated and 5-capped. Genes are expressed in an ordered cascade. Early genes are expressed prior to DNA replication; expression of late genes is dependent on the onset of DNA replication. Synthesis of some early genes continues throughout infection. Intermediate genes are expressed late but their expression does not depend on the onset of DNA replication. Promoter elements are relatively short and located immediately upstream to ORFs; transcription start sites are generally a short distance from start codons. No consensus sequence for African swine fever virus (ASFV) promoters is available. Both early and late gene transcripts are of defined length; sequences of seven or more consecutive thymidylate residues in the coding strand are signals for mRNA 3-end formation.

Several structural proteins are expressed as polyproteins and cleaved at the sequence GlyGlyX. The polyprotein with Mr 220 10³ is myristylated. Other virus encoded proteins are modified by phosphorylation (p10, p32), and N-linked glycosylation.

Virus morphogenesis takes place in virus factories; these are rich in fibrillar and membranous material. Two layers of membrane derived from the endoplasmic reticulum are incorporated as internal lipid membranes. Formation of the icosahedral capsid is thought to occur on these membranes. The virus genome and enzymes are packaged into a nucleoprotein core. Extracellular virus has a loose fitting external lipid envelope possibly derived by budding through the plasma membrane.

Antigenic Properties

Infected swine mount a protective immune response against non-fatal virus strains and produce antibodies. Antibodies can neutralise virus strains with a low number of passages in tissue culture but are not as effective against virus with a high number of passages. This difference may be caused by changes in virus phospholipids. Antibodies against proteins p72, p12, p30 and p54 neutralise virus, those against p30 inhibit virus internalization rather than attachment. Monoclonal antibody analyses show that structural proteins p150, p14 and p12 vary between isolates. Several virus encoded proteins (for example p54 or j13L and B602L or 9RL) contain tandem repeat arrays which vary in number and sequence when genomes of different isolates are compared.

Biological Properties

African swine fever virus infects domestic and wild swine (Sus scrofa domesticus and S. s. ferus), warthogs (Phacochoerus aethiopicus) and bushpigs (Potamochoerus porcus). Disease signs are only apparent in domestic and wild swine. Soft ticks of the genus Ornithodoros are also infected and O. moubata acts as a vector in parts of Africa south of the Sahara and O. erraticus acted as a vector in southwestern Spain and Portugal. Virus can be transmitted in ticks transstadially, transovarially and sexually. Warthogs, bushpigs and swine can be infected by bites from infected ticks. Neither vertical nor horizontal transfer of virus between warthogs is thought to occur. However, transmission between domestic swine can occur by direct contact, or by ingestion of infected meat, or fomites, or mechanically by biting flies. Warthogs, bushpigs, wild swine and ticks act as reservoirs of virus. Disease is endemic in domestic swine in many African countries and in Sardinia. Disease was first introduced into Europe in Portugal in 1957 and was endemic in parts of the Iberian peninsula from 1960 until 1995. Sporadic outbreaks have occurred in and been eradicated from Belgium, Brazil, Cuba, the Dominican Republic, France, Haiti, Holland and Malta. Virus isolates differ in virulence and may produce a variety of signs ranging from acute to chronic to inapparent. Virulent isolates may cause 100% mortality in 7 to 10 days. Less virulent isolates may produce a mild disease from which a number of infected swine recover and become carriers. Viruses replicate in cells of the mononuclear phagocytic system and reticulo-endothelial cells in lymphoid tissues and organs of domestic swine. Widespread cell death in lymphoid tissues and damage to endothelial cells in arterioles and capillaries account for the lesions seen in acute disease.

List of Species Demarcation Criteria

Not applicable.

List of Species in the Genus

Official virus species names are in italics. Tentative virus species names, alternative names ( ), strains or serotypes are not italicized. The virus name and assigned abbreviation ( ) are:

Species in the Genus

African swine fever virus

(ASFV)

Tentative Species in the Genus

None reported.

Phylogenetic Relationships within the Family

Not applicable.

Similarity with Other Taxa

Earlier African swine fever virus was listed as a member of the family Iridoviridae, but as more information was obtained, it was removed from this family and placed as the only member of a separate genus “African swine fever-like viruses”. Additionally, the virus exhibits some similarities in genome structure and strategy of replication to the poxviruses and phycodnaviruses, but it has a quite different virion structure from the poxviruses and many other properties that distinguish it from the member viruses of the families Poxviridae and Phycodnaviridae.

Derivation of Names

Asfar sigla: derived from African swine fever and related viruses.