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Pires, Sandra; Ribeiro, Graça; Costa, João

doi:10.1023/a:1007992806818

Cited by 26 publications

(14 citation statements)

References 13 publications

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“…Among the 26 genes missing from the viral genome, thirteen belong to the multigene family MGF110 (1L-14L) 9 , 10 and three to the MGF360 (1L-3L). While the specific functions of these genes are unknown 11 , it was shown that members of the MGF110 carry C-Terminal KDEL endoplasmic reticulum retention motifs and might be involved in preparing the ER for viral morphogenesis 12 .…”

Section: Discussionmentioning

confidence: 99%

Deletion at the 5’-end of Estonian ASFV strains associated with an attenuated phenotype

Zani

Forth

et al. 2018

Sci Rep

143

141

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African swine fever (ASF) was introduced into the Eastern European Union in 2014 and led to considerable mortality among wild boar. In contrast, unexpected high antibody prevalence was reported in hunted wild boar in north-eastern Estonia. One of the causative virus strains was recently characterized. While it still showed rather high virulence in the majority of experimentally infected animals, one animal survived and recovered completely. Here, we report on the follow-up characterization of the isolate obtained from the survivor in the acute phase of infection. As a first step, three in vivo experiments were performed with different types of pigs: twelve minipigs (trial A), five domestic pigs (trial B), and five wild boar (trial C) were inoculated. 75% of the minipigs and all domestic pigs recovered after an acute course of disease. However, all wild boar succumbed to infection within 17 days. Representative samples were sequenced using NGS-technologies, and whole-genomes were compared to ASFV “Georgia 2007/1”. The alignments indicated a deletion of 14560 base pairs at the 5’ end, and genome reorganization by duplication. The characteristic deletion was confirmed in all trial samples and local field samples. In conclusion, an ASFV variant was found in Estonia that showed reduced virulence.

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Section: Discussionmentioning

confidence: 99%

Deletion at the 5’-end of Estonian ASFV strains associated with an attenuated phenotype

Zani

Forth

et al. 2018

Sci Rep

143

141

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“…Those findings suggest that development of attenuated ASFV recombinant viruses by genetic manipulations of a specific gene(s) is an effective approach for vaccine development. The MGF360 and MGF505 genes exist in the highly variable left-terminal region of the ASFV genome and have been the focus of investigation since some naturally attenuated field isolates such as OURT 88/3 or NHV (37), or cell-culture adapted attenuated ASFV strains such as BA71v (15,(19)(20)(21) or ASFV-G/V110 (22), presented similar deletions in this region encompassing members of both MGFs (Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

“…Some cell culture-adapted ASFV isolates (such as the Vero celladapted Badajoz71 or Georgia07 isolates) contain gaps in the variable left-terminal region of their genomes harboring deletions that encompass several genes of both MGF360 and MGF505 (15,(19)(20)(21)(22). Usually, adaptation to replication in these cell lines coincides with attenuation of these isolates in swine (8,(22)(23)(24)(25).…”

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confidence: 99%

African Swine Fever Virus Georgia Isolate Harboring Deletions of MGF360 and MGF505 Genes Is Attenuated in Swine and Confers Protection against Challenge with Virulent Parental Virus

O’Donnell

Holinka

Gladue

et al. 2015

J Virol

286

285

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African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The control of African swine fever (ASF) has been hampered by the unavailability of vaccines. Experimental vaccines have been developed using genetically modified live attenuated ASFVs where viral genes involved in virus virulence were removed from the genome. Multigene family 360 (MGF360) and MGF505 represent a group of genes sharing partial sequence and structural identities that have been connected with ASFV host range specificity, blocking of the host innate response, and virus virulence. Here we report the construction of a recombinant virus (ASFV-G-⌬MGF) derived from the highly virulent ASFV Georgia 2007 isolate (ASFV-G) by specifically deleting six genes belonging to MGF360 or MGF505: MGF505-1R, MGF360-12L, MGF360-13L, MGF360-14L, MGF505-2R, and MGF505-3R. ASFV-G-⌬MGF replicates as efficiently in primary swine macrophage cell cultures as the parental virus. In vivo, ASFV-G-⌬MGF is completely attenuated in swine, since pigs inoculated intramuscularly (i.m.) with either 10 2 or 10 4 50% hemadsorbing doses (HAD 50 ) remained healthy, without signs of the disease. Importantly, when these animals were subsequently exposed to highly virulent parental ASFV-G, no signs of the disease were observed, although a proportion of these animals harbored the challenge virus. This is the first report demonstrating the role of MGF genes acting as independent determinants of ASFV virulence. Additionally, ASFV-G-⌬MGF is the first experimental vaccine reported to induce protection in pigs challenged with highly virulent and epidemiologically relevant ASFV-G. A frican swine fever (ASF) is a contagious viral disease of swine caused by ASF virus (ASFV), a large enveloped virus containing a double-stranded DNA genome of approximately 180 to 190 kbp (1). ASF causes a spectrum of disease manifestations, from highly lethal to subclinical, depending on host characteristics and the virus strain (2). Virulent ASFV infections in domestic pigs are fatal and characterized by fever, hemorrhages, ataxia, and severe depression.Currently, ASF is endemic in several sub-Saharan African countries. In Europe, the disease is endemic in Sardinia (Italy), and outbreaks have been recorded in the Caucasus region since 2007, affecting Georgia, Armenia, Azerbaijan, and Russia, and, more recently, in Ukraine, Belarus, Lithuania, Latvia, and Poland, threatening to disseminate into neighboring western European countries (3).There is no vaccine available for ASF, and outbreaks are usually controlled by animal quarantine and elimination of the affected animals. Experimental vaccines based on the use of different inactivated virus preparations have failed to induce protective immunity (4-6). Protective immunity against reinfection with homologous viruses and (rarely) against reinfection with heterologous viruses does develop in pigs surviving viral infection (7,8). Pigs im...

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“…The process of ASFV adaptation to be able to replicate in established cell lines is usually accompanied by attenuation of virulence and significant modifications of the viral genome, generally affecting the variable genomic ends (21,22,23,24,25). Unfortunately, in most of these cases, detailed descriptions of the adaptation process and the associated genetic and phenotypic changes of ASFV are not readily available.…”

Section: Discussionmentioning

confidence: 99%

The Progressive Adaptation of a Georgian Isolate of African Swine Fever Virus to Vero Cells Leads to a Gradual Attenuation of Virulence in Swine Corresponding to Major Modifications of the Viral Genome

Krug

Holinka

O’Donnell

et al. 2015

J Virol

148

159

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African swine fever virus (ASFV) causes a contagious and often lethal disease of feral and domestic swine. Experimental vaccines derived from naturally occurring, genetically modified, or cell culture-adapted ASFV have been evaluated, but no commercial vaccine is available to control African swine fever (ASF). We report here the genotypic and phenotypic analysis of viruses obtained at different passages during the process of adaptation of a virulent ASFV field isolate from the Republic of Georgia (ASFV-G) to grow in cultured cell lines. ASFV-G was successively passaged 110 times in Vero cells. Viruses obtained at passages 30, 60, 80, and 110 were evaluated in vitro for the ability to replicate in Vero cells and primary swine macrophages cultures and in vivo for assessing virulence in swine. Replication of ASFV-G in Vero cells increased with successive passages, corresponding to a decreased replication in primary swine macrophages cultures. In vivo, progressive loss of virus virulence was observed with increased passages in Vero cells, and complete attenuation of ASFV-G was observed at passage 110. Infection of swine with the fully attenuated virus did not confer protection against challenge with virulent parental ASFV-G. Full-length sequence analysis of each of these viruses revealed significant deletions that gradually accumulated in specific areas at the right and left variable ends of the genome. Mutations that result in amino acid substitutions and frameshift mutations were also observed, though in a rather limited number of genes. The potential importance of these genetic changes in virus adaptation/attenuation is discussed. IMPORTANCEThe main problem in controlling ASF is the lack of vaccines. Attempts to produce vaccines by adaptation of ASFV to cultured cell lines have been made. These attempts led to the production of attenuated viruses that conferred only homologous protection. Specifics regarding adaptation of these isolates to cell cultures have been insufficiently described. Details like the numbers of passages required to obtain attenuated viruses, genetic modifications introduced into the virus genomes along passages, and the extent of attenuation and induced protective efficacy are not readily available. In this study, we assessed the changes that lead to decreased growth in swine macrophages and to attenuation in swine. Loss of virulence, probably associated with limited replication in vivo, may lead to the lack of protective immunity in swine observed after challenge. This report provides valuable information that can be used to further the understanding of ASFV gene function, virus attenuation, and protection against infection.A frican swine fever (ASF) is a contagious disease of swine caused by ASF virus (ASFV), an enveloped virus containing a large (190-kbp) double-stranded DNA (dsDNA) genome. ASFV infection of domestic pigs can induce a spectrum of disease severity, from highly lethal to subclinical, depending on host characteristics and the particular circulating virus strain (1).A...

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Cited by 26 publications

References 13 publications

Deletion at the 5’-end of Estonian ASFV strains associated with an attenuated phenotype

Deletion at the 5’-end of Estonian ASFV strains associated with an attenuated phenotype

African Swine Fever Virus Georgia Isolate Harboring Deletions of MGF360 and MGF505 Genes Is Attenuated in Swine and Confers Protection against Challenge with Virulent Parental Virus

The Progressive Adaptation of a Georgian Isolate of African Swine Fever Virus to Vero Cells Leads to a Gradual Attenuation of Virulence in Swine Corresponding to Major Modifications of the Viral Genome

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