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Forth, J. H.

Publications and source records attributed to Forth, J. H..

3 recordsLinked to original sources

Full genome sequence analysis of African swine fever virus isolates from Cameroon

African swine fever is a devastating disease of domestic pigs that has spread across the globe since its introduction into Georgia in 2007. The etiological agent is a large double-stranded DNA virus with a genome of 170 to 180 kb in length depending on the isolate. Much of the differences in genome length between isolates are due to variations in the copy number of five different multigene families that are encoded in repetitive regions that are towards the termini of the covalently closed ends of the genome. Molecular epidemiology of ASFV is primarily based on Sanger sequencing of a few conserved and variable regions, but due to the stability of the dsDNA genome changes in the variable regions occur relatively slowly. Observations in Europe and Asia have shown that changes in other genetic loci can occur and that this could be useful in molecular tracking. ASFV has been circulating in Western Africa for at least forty years. It is therefore reasonable to assume that changes may have accumulated in regions of the genome other than the standard targets over the years. At present only one full genome sequence is available for an isolate from Western Africa, that of a highly virulent isolate collected from Benin during an outbreak in 1997. In Cameroon, ASFV was first reported in 1981 and outbreaks have been reported to the present day and is considered endemic. Here we report three full genome sequences from Cameroon isolates of 1982, 1994 and 2018 outbreaks and identify novel single nucleotide polymorphisms and insertion-deletions that may prove useful for molecular epidemiology studies in Western Africa and beyond.

microbiology↗

African swine fever virus - variants on the rise

African swine fever virus (ASFV), a large and complex DNA-virus circulating between soft ticks and indigenous suids in sub-Saharan Africa, has made its way into swine populations from Europe to Asia. This virus, causing a severe haemorrhagic disease (African swine fever) with very high lethality rates in wild boar and domestic pigs, has demonstrated a remarkably high genetic stability for over 10 years. Consequently, analyses into virus evolution and molecular epidemiology often struggled to provide the genetic basis to trace outbreaks while few resources have been dedicated to genomic surveillance on whole-genome level. During its recent incursion into Germany in 2020, ASFV has unexpectedly diverged into five clearly distinguishable linages with at least ten different variants characterized by high-impact mutations never identified before. Noticeably, all new variants share a frameshift mutation in the 3 end of the DNA polymerase PolX gene O174L, suggesting a causative role as possible mutator gene. Although epidemiological modelling supported the influence of increased mutation rates, it remains unknown how fast virus evolution might progress under these circumstances. Moreover, a tailored Sanger sequencing approach allowed us, for the first time, to trace variants with genomic epidemiology to regional clusters. In conclusion, our findings suggest that this new factor has the potential to dramatically influence the course of the ASFV pandemic with unknown outcome. Therefore, our work highlights the importance of genomic surveillance of ASFV on whole-genome level, the need for high-quality sequences and calls for a closer monitoring of future phenotypic changes of ASFV.

genomics↗

African swine fever virus-like integrated elements in a soft tick genome - an ancient virus vector arms race?

BackgroundAfrican swine fever virus (ASFV) is the only known DNA-arbovirus and a most devastating suid pathogen that, originating from a sylvatic cycle in Africa, has spread to eastern Europe and recently reached western Europe and Asia, leading to a socio-economic crisis of global proportion. However, since neither closely related viruses nor integrated viral elements have yet been identified, ASFV evolution remains a mystery. ResultsHere, we show that soft ticks of the Ornithodoros moubata group, the natural arthropod vector of ASFV, harbour African swine fever virus-like integrated (ASFLI)-elements corresponding to up to 10% (over 20 kb) of the ASFV genome. Through orthologous dating and molecular clock analyses, we provide data suggesting that integration occurred over 1.47 million years ago. Furthermore, our data indicate that these elements, showing high sequence identities to modern ASFV, are maintained in the tick genome to protect the tick from infection with specific ASFV-strains through RNA interference. ConclusionWe suggest that this mechanism of protection, shaped through many years of co-evolution, is part of an evolutionary virus-vector "arms race", a finding that has not only high impact on our understanding of the co-evolution of viruses with their hosts but also provides a glimpse into the evolution of ASFV.

microbiology↗