Biology subjects

Blome, S.

Publications and source records attributed to Blome, S..

5 recordsLinked to original sources

bioRxiv2025

Duration of immunity following infection with moderately virulent ASFV

African swine fever virus (ASFV) poses a significant threat to pork production and wild pig populations worldwide. The study assessed the long-term fate and immunity of animals recovering from a moderately virulent ASFV infection, following the principles of a duration of immunity study for live vaccines. Pigs inoculated with the moderately virulent ASFV strain Estonia14 largely developed mild clinical signs and only transient viremia. Six months after the initial inoculation and once fully recovered, all the animals were challenged with highly virulent ASFV Armenia08. Only one of the previously exposed pigs exhibited mild clinical signs, while all control animals showed typical signs of acute, lethal ASF. Moreover, only a subset of pigs inoculated with the ASF strain Estonia14 displayed temporary detectability of ASFV genomes following challenge infection. Virus isolation corroborated these findings, with low levels of infectious virus in organs of previously inoculated pigs (28 days post challenge). Furthermore, monitoring of IgM and IgG kinetics enabled the analysis of humoral responses. IgG levels were sustained over the study period and increased slightly upon challenge infection. Lastly, plasma analysis revealed elevated complement factor C3a levels post inoculation and challenge in the recovered pigs, directly correlating with challenge virus presence. In contrast, both C3a and C5a levels were increased in the control group. It could be shown that complement system activation was mediated by the lectin pathway, possibly by interaction of mannose-binding lectins and ASFV particles. This study suggests that protective immunity following recovery can last at least six months. No cases of persistent or chronic disease were observed in convalescent pigs. These findings have implications for both vaccine development and assessment, as well as for disease control strategies including surveillance actions.

immunology↗

bioRxiv2022

Pathology of African Swine Fever in wild boar naturally infected with German virus variants

In 2020, African swine fever (ASF) was first notified in German wild boar, reaching a case number of about 4200 to date. Upon experimental infection, pathology is well-documented, however, data on field infections are very scarce in domestic pigs and not available from wild boar, respectively. Although ASF viral genome is considered exceptionally stable, a total of five lineages with 10 distinct virus variants of genotype II have emerged in Eastern Germany. To investigate the pathology in naturally infected wild boar and to evaluate virus variants II, III and IV for their virulence, wild boar carcasses were obtained from three different outbreak areas. The cadavers underwent virological and pathomorphological investigation. Regardless of the virus variant all wild boar revealed characteristic lesions of highest severity indicative for ASF. However, wild boar infected with variant IV from Spree-Nei{beta}e (SN) district showed lower viral genome loads and a lower total viral antigen score, but simultaneously revealed more chronic lesions. Our findings indicate a protracted course of the disease at least after infection with variant IV, but need confirmation under standardized experimental conditions. There is a strong need to monitor differences in the virulence among variants to identify potential attenuation that might complicate diagnosis.

pathology↗

bioRxiv2022

CP204L Is a Multifunctional Protein of African Swine Fever Virus That Interacts with The VPS39 Subunit of HOPS Complex and Promotes Lysosome Clustering

Virus replication depends on a complex interplay between viral and host proteins. In the case of African swine fever virus (ASFV), a large DNA virus, only few virus-host protein-protein interactions have been identified to date. In this study, we demonstrate that the ASFV protein CP204L directly interacts with the cellular homotypic fusion and protein sorting (HOPS) protein VPS39, blocking its association with the lysosomal HOPS complex, that modulates endolysosomal trafficking and promotes lysosome clustering. Instead, VPS39 is targeted to the sites of virus replication termed virus factories. Furthermore, we show that loss of VPS39 reduces the levels of virus proteins synthesized in the early phase of infection and delays ASFV replication but does not completely inhibit it. Collectively, these results identify a novel virus-host protein interaction that modulates host membrane rearrangement during infection and provide evidence that CP204L is a multifunctional protein engaged in distinct steps of the ASFV life cycle. ImportanceAfrican swine fever virus (ASFV) was first identified over a hundred years ago. Since then, much effort has been made to understand the pathogenesis of ASFV. Yet, the specific roles of many individual ASFV proteins during the infection remain enigmatic. This study provides evidence that CP204L, one of the most abundant ASFV proteins, modulates endosomal trafficking during virus infection. Through direct protein-protein interaction, CP204L prevents the recruitment of VPS39 to the endosomal and lysosomal membranes, resulting in their accumulation. Consequently, CP204L and VPS39 become sequestered to the ASFV replication site. These results uncover a novel function of viral protein CP204L and extend our understanding of complex interaction between virus and host.

microbiology↗

bioRxiv2022

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↗

bioRxiv2020

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↗