The Genetics of Life and Death: Virus-Host Interactions Underpinning Resistance to African Swine Fever, a Viral Hemorrhagic Disease

Abstract

Pathogen transmission from wildlife hosts to genetically distinct species is a major driver of disease emergence. African swine fever virus (ASFV) persists in sub-Saharan Africa through a sylvatic cycle between warthogs and soft ticks that infest their burrows. The virus does not cause disease in these animals, however transmission of the virus to domestic pigs or wild boar causes a hemorrhagic fever that is invariably fatal. ASFV transmits readily between domestic pigs and causes economic hardship in areas where it is endemic. The virus is also a significant transboundary pathogen that has become established in Eastern Europe, and has recently appeared in China increasing the risk of an introduction of the disease to other pig producing centers. Although a DNA genome mitigates against rapid adaptation of the virus to new hosts, extended epidemics of African swine fever (ASF) can lead to the emergence of viruses with reduced virulence. Attenuation in the field leads to large deletions of genetic material encoding genes involved in modulating host immune responses. Therefore resistance to disease and tolerance of ASFV replication can be dependent on both virus and host factors. Here we describe the different virus-host interfaces and discuss progress toward understanding the genetic determinants of disease outcome after infection with ASFV.

Keywords: African swine fever virus (ASFV); DNA virus infection; Ornithodoros; host resistance; host tolerance; interferon; viral hemorrhagic fever; warthog.

FIGURE 1

The epidemiologic cycles of African swine fever and main transmission agents. (1) Sylvatic cycle: the common warthog (Phacochoerus africanus), bushpig (Potamochoerus larvatus), and soft ticks of Ornithodoros spp. The role of the bushpig in the sylvatic cycle remains unclear. (2) The tick–pig cycle: soft ticks and domestic pigs (Sus scrofa domesticus). (3) The domestic cycle: domestic pigs and pig-derived products (pork, blood, fat, lard, bones, bone marrow, hides). (4) The wild boar–habitat cycle: wild boar (S. scrofa), pig-, and wild boar–derived products and carcasses, and the habitat. Reproduced with kind permission from Chenais et al. (2018).

FIGURE 2

Neighbor-Joining phylogenetic tree of representative ASFV isolates. The evolutionary history was inferred using the Neighbor–Joining method. The optimal tree with the sum of branch length = 0.29203136 is shown. The bootstrap test values (i.e., percentage of replicate trees in which the associated taxa clustered together, 1000 replicates) are shown next to the nodes. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The evolutionary distances were computed using the Kimura 2-parameter method and are in the units of the number of base substitutions per site. The analysis involved 47 nucleotide sequences. All positions containing gaps and missing data were eliminated. There were a total of 399 positions in the final dataset. Evolutionary analyses were conducted in MEGA7 (Kumar et al., 2016). Symbols indicate isolates shown in Figure 3, all other isolates were obtained from domestic pigs. L1, L2, and L3 indicate the lineages identified by Boshoff et al. (2007). Full details of these isolates are provided in Supplementary Table S1.

FIGURE 3

Relationship between distribution of host species and diversity of ASFV. Map of sub-Saharan Africa showing the distribution of bushpigs and red river hogs (Potamochoerus spp.), common and desert warthog (Phacochoerus spp.) and the giant forest hog. ASFV isolates for which the genotype has been determined are indicated by colored symbols. ASFV isolates from soft ticks (Ornithodoros moubata complex) are also indicated. Tick isolates were collected from warthog burrows, with the exception of the two genotype VIII isolates from Malawi and isolates of genotype II and XXIV from Mozambique which were collected from pig holdings. Each symbol indicates a single location which may represent up to 11 separate isolates, full details of these are provided in Supplementary Table S2. The positions of some symbols have been moved to aid clarity where multiple genotypes or hosts have been identified at the same sites.