Repair of Viral Genomes by Base Excision Pathways: African Swine Fever Virus as a Paradigm

Abstract

African swine fever virus (ASFV) is an enveloped deoxyvirus that infects suids and causes a fatal disease in domestic pigs. ASFV also propagates in ticks of the genus Ornithodoros, being the only known DNA arbovirus. Because of its unique features, ASFV is the sole member of the Asfaviridae family (Salas 1999; Dixon and Chapman 2008), although comparative genome analyses suggest that ASFV shares a common origin with the members of the proposed nucleocytoplasmic large DNA viruses (NCLDVs), along with poxviruses, iridoviruses and mimivirus, among others (Iyer et al. 2001; Iyer et al. 2006). The disease, African swine fever (ASF), was reported for the first time in Kenya in the 1920s, as an acute hemorrhagic syndrome of domestic pigs (Montgomery 1921). The infection spread outside Africa to the Iberian Peninsula, initially to Portugal in 1957 and 1960, and subsequently to Spain and several other countries in Europe and Latin America. The virus has been eradicated from all of these regions, apart from sub-Saharan Africa countries and the Mediterranean island Sardinia, where the disease remains enzootic (Gomez-Tejedor Ortiz 1993). In 2007, a new transcontinental spread of ASF occurred with the introduction of ASF to Georgia in the Caucasus region (Beltran-Alcrudo et al. 2008; Chapman et al. 2008; Rowlands et al. 2008), followed by widespread distribution to neighboring countries, including Armenia, Azerbaijan and several territories in Russia. Currently there is no vaccine available for ASF and the disease is controlled only by animal quarantine and slaughter. Therefore, ASF has potentially devastating effects on the commercial and subsistence pig production sectors, particularly in developing countries (Costard et al. 2009). The virus particle has an overall icosahedral shape and an average diameter of 200 nm. The ASFV genome is a double-stranded DNA molecule of 170 to 190 kbp, structured in a central constant region of about 125 kbp and two variable regions at the ends (Blasco et al. 1989). The two strands are covalently closed, at both ends, by a 37 nucleotide-long hairpin loops, followed by a perfect terminal inverted repeat (TIR). A comparison of restriction maps of different ASFV isolates has shown that the two variable regions show deletion or additions