Pathogenesis of African swine fever in domestic pigs and European wild boar

Blome, Sandra; Gabriel, Claudia; Beer, Martin

doi:10.1016/j.virusres.2012.10.026

Cited by 288 publications

(267 citation statements)

References 81 publications

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“…Circulating strains with different levels of virulence cause a broad range of clinical symptoms in susceptible domestic swine and European wild boar, ranging from peracute and acute forms, with haemorrhagic fever and death within a few days, to chronic or even unapparent disease (Blome et al, 2013). The underlying mechanisms are far from being fully understood.…”

Section: Introductionmentioning

confidence: 99%

Related strains of African swine fever virus with different virulence: genome comparison and analysis

Portugal

Coelho

Höper

et al. 2015

Journal of General Virology

112

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Section: Introductionmentioning

confidence: 99%

Related strains of African swine fever virus with different virulence: genome comparison and analysis

Portugal

Coelho

Höper

et al. 2015

Journal of General Virology

112

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“…While warthogs and bushpigs are asymptomatic carriers of the disease, acting as reservoirs of infection, the clinical signs in domestic pigs and wild boars may vary from acute to chronic forms, depending on the virulence of the ASFV strain and on the immunological status of the host (3,4).…”

mentioning

confidence: 99%

DNA-Binding Properties of African Swine Fever Virus pA104R, a Histone-Like Protein Involved in Viral Replication and Transcription

Frouco

Freitas

Coelho

et al. 2017

J Virol

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African swine fever virus (ASFV) codes for a putative histone-like protein (pA104R) with extensive sequence homology to bacterial proteins that are implicated in genome replication and packaging. Functional characterization of purified recombinant pA104R revealed that it binds to single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) over a wide range of temperatures, pH values, and salt concentrations and in an ATP-independent manner, with an estimated binding site size of about 14 to 16 nucleotides. Using site-directed mutagenesis, the arginine located in pA104R's DNA-binding domain, at position 69, was found to be relevant for efficient DNA-binding activity. Together, pA104R and ASFV topoisomerase II (pP1192R) display DNA-supercoiling activity, although none of the proteins by themselves do, indicating that the two cooperate in this process. In ASFV-infected cells, A104R transcripts were detected from 2 h postinfection (hpi) onward, reaching a maximum concentration around 16 hpi. pA104R was detected from 12 hpi onward, localizing with viral DNA replication sites and being found exclusively in the Tritoninsoluble fraction. Small interfering RNA (siRNA) knockdown experiments revealed that pA104R plays a critical role in viral DNA replication and gene expression, with transfected cells showing lower viral progeny numbers (up to a reduction of 82.0%), lower copy numbers of viral genomes (Ϫ78.3%), and reduced transcription of a late viral gene (Ϫ47.6%). Taken together, our results strongly suggest that pA104R participates in the modulation of viral DNA topology, probably being involved in viral DNA replication, transcription, and packaging, emphasizing that ASFV mutants lacking the A104R gene could be used as a strategy to develop a vaccine against ASFV.IMPORTANCE Recently reintroduced in Europe, African swine fever virus (ASFV) causes a fatal disease in domestic pigs, causing high economic losses in affected countries, as no vaccine or treatment is currently available. Remarkably, ASFV is the only known mammalian virus that putatively codes for a histone-like protein (pA104R) that shares extensive sequence homology with bacterial histone-like proteins. In this study, we characterized the DNA-binding properties of pA104R, analyzed the functional importance of two conserved residues, and showed that pA104R and ASFV topoisomerase II cooperate and display DNA-supercoiling activity. Moreover, pA104R is expressed during the late phase of infection and accumulates in viral DNA replication sites, and its downregulation revealed that pA104R is required for viral DNA replication and transcription. These results suggest that pA104R participates in the modulation of viral DNA topology and genome packaging, indicating that A104R deletion mutants may be a good strategy for vaccine development against ASFV.

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“…S. Blum et al conducted a study using high, moderate and low infection doses of ASFV Caucasian strains to assess the risk of development of chronic disease and virus infection. They showed that low dose infection may lead to prolonged incubation periods and clinical courses, and that 1000 HAD are not sufficient to produce disease in healthy wild boars [6,7].…”

Section: Discussionmentioning

confidence: 99%

Biological properties of African swine fever virus Odintsovo 02/14 isolate and its genome analysis

Yelsukova¹,

Шевченко²,

Варенцова³

et al. 2017

IJOEAR

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Pathogenesis of African swine fever in domestic pigs and European wild boar

Cited by 288 publications

References 81 publications

Related strains of African swine fever virus with different virulence: genome comparison and analysis

Related strains of African swine fever virus with different virulence: genome comparison and analysis

DNA-Binding Properties of African Swine Fever Virus pA104R, a Histone-Like Protein Involved in Viral Replication and Transcription

Biological properties of African swine fever virus Odintsovo 02/14 isolate and its genome analysis

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