African Swine Fever Virus: An Emerging DNA Arbovirus

Abstract

African swine fever virus (ASFV) is the sole member of the family Asfarviridae, and the only known DNA arbovirus. Since its identification in Kenya in 1921, ASFV has remained endemic in Africa, maintained in a sylvatic cycle between Ornithodoros soft ticks and warthogs (Phacochoerus africanus) which do not develop clinical disease with ASFV infection. However, ASFV causes a devastating and economically significant disease of domestic (Sus scrofa domesticus) and feral (Sus scrofa ferus) swine. There is no ASFV vaccine available, and current control measures consist of strict animal quarantine and culling procedures. The virus is highly stable and easily spreads by infected swine, contaminated pork products and fomites, or via transmission by the Ornithodoros vector. Competent Ornithodoros argasid soft tick vectors are known to exist not only in Africa, but also in parts of Europe and the Americas. Once ASFV is established in the argasid soft tick vector, eradication can be difficult due to the long lifespan of Ornithodoros ticks and their proclivity to inhabit the burrows of warthogs or pens and shelters of domestic pigs. Establishment of endemic ASFV infections in wild boar populations further complicates the control of ASF. Between the late 1950s and early 1980s, ASFV emerged in Europe, Russia and South America, but was mostly eradicated by the mid-1990s. In 2007, a highly virulent genotype II ASFV strain emerged in the Caucasus region and subsequently spread into the Russian Federation and Europe, where it has continued to circulate and spread. Most recently, ASFV emerged in China and has now spread to several neighboring countries in Southeast Asia. The high morbidity and mortality associated with ASFV, the lack of an efficacious vaccine, and the complex makeup of the ASFV virion and genome as well as its lifecycle, make this pathogen a serious threat to the global swine industry and national economies. Topics covered by this review include factors important for ASFV infection, replication, maintenance, and transmission, with attention to the role of the argasid tick vector and the sylvatic transmission cycle, current and future control strategies for ASF, and knowledge gaps regarding the virus itself, its vector and host species.

Keywords: African swine fever virus; DNA arbovirus; domestic swine; soft tick; transmission; virus replication; wild boar.

Figure 1

Recent ASF status in Europe, Asia, and Africa. (A) Eurasian Epidemic, 2007-September 2019: Within European nations, continuing outbreaks (yellow) are reported in Sardinia, Belgium, Bulgaria, Hungary, Latvia, Moldova, Poland, Romania, Slovakia, Serbia, Russian Federation, and Ukraine. Resolved outbreaks (blue) are reported for Belarus, Czech Republic, Estonia, and Lithuania. (B) Transcaucasus and Asian Epidemic, 2007-September 2019: Continuing outbreaks (yellow) are reported in People's Republic of China, Democratic People's Republic of Korea, Lao People's Democratic Republic, Myanmar, The Philippines, Russian Federation, Republic of Korea, and Vietnam. Resolved outbreaks (blue) include Armenia, Azerbaijan, Cambodia, Republic of Georgia, and Mongolia. (C) African Nations with OIE-Notified ASF Outbreaks Since 2018: Countries which have notified the OIE of the presence of ASF from 2018 through September 2019 include Benin, Burkina Faso, Burundi, Cabo Verde, Central African Republic, Democratic Republic of the Congo, Gambia, Ghana, Guinea-Bissau, Madagascar, Malawi, Mozambique, Namibia, Nigeria, Rwanda, Senegal, Sierra Leone, South Africa, Tanzania, Togo, Uganda, Zambia, and Zimbabwe. Source: OIE WAHIS African Swine Fever (ASF) Report: September 13–26, 2019.

Figure 2

Schematic of ASFV transmission cycles. In Europe, Asia, and Africa, ASFV is readily transmissible between domestic pigs through direct contact and contaminated pork products and fomites. (A) In Europe and Asia, two-way transmission between pigs and boars can occur at the livestock-wildlife interface, especially where poor farm biosecurity exists. Transmission between wild boar is capable of maintaining and spreading the virus across large geographic areas. ASFV can be transmitted between soft ticks of the Ornithodoros erraticus complex and domestic swine, and soft ticks can serve as persistent reservoirs for the virus as seen in the Iberian Peninsula. There is little evidence to support transmission between soft ticks and Eurasian wild boar and domestic pigs in contemporary European and Asian epidemics. (B) The sylvatic cycle in Africa involves virus transmission between juvenile warthogs (Phacochoerus africanus) and soft ticks of the Ornithodoros moubata complex. Infected ticks transmit ASFV to juvenile warthogs when taking a blood meal, and uninfected ticks are infected after feeding on viremic juvenile warthogs, while adult warthogs typically do not maintain high levels of viremia and are dead-end hosts. (C) Within soft ticks of the O. moubata and O. erraticus complexes, virus is transmitted via sexual and transovarial routes and can be maintained across multiple life stages.

Figure 3

ASFV replication cycle. (A) ASFV entry is primarily mediated through an unknown receptor and/or macropinocytosis; Fc-receptor mediated entry and phagocytosis have also been suggested entry mechanisms. (B) The virus is then trafficked through early endosomes or macropinosomes to late endosomes, where viral uncoating takes place via endosomal acidification. (C) Viral replication takes place in the cytoplasm in viral factories, with brief replication events occurring in the nucleus. Gene expression occurs temporally, first with early genes to produce replication proteins, followed by intermediate and late genes that produce structural proteins that are assembled into the virion. (D) Virions are assembled and bud from the infected cell within 24 hpi. Known major host (orange dots) and viral (blue diamonds) factors involved in the ASFV replication cycle, which are discussed in the text, are indicated. ASFV, African swine fever virus; mpi, minutes post-infection; hpi, hours post-infection; vRNApol, viral RNA polymerase; vDNApol, viral DNA polymerase; PI3K, phosphoinositide-3-kinase; Rac1, Rac-1 Rho-GTPase; Pak1, Pak-1 kinase; PtdIns3P, phosphatidylinositol-3-phosphate; PtdIns (4, 6); P2, biphosphate PtdIns (4, 6) diphosphorus.