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In silico structural and functional prediction of African swine fever virus protein-B263R reveals features of a TATA-binding protein.

ABSTRACT: African swine fever virus (ASFV) is the etiological agent of ASF, a fatal hemorrhagic fever that affects domestic pigs. There is currently no vaccine against ASFV, making it a significant threat to the pork industry. The ASFV genome sequence has been published; however, about half of ASFV open reading frames have not been characterized in terms of their structure and function despite being essential for our understanding of ASFV pathogenicity. The present study reports the three-dimensional structure and function of uncharacterized protein, pB263R (NP_042780.1), an open reading frame found in all ASFV strains. Sequence-based profiling and hidden Markov model search methods were used to identify remote pB263R homologs. Iterative Threading ASSEmbly Refinement (I-TASSER) was used to model the three-dimensional structure of pB263R. The posterior probability of fold family assignment was calculated using TM-fold, and biological function was assigned using TM-site, RaptorXBinding, Gene Ontology, and TM-align. Our results suggests that pB263R has the features of a TATA-binding protein and is thus likely to be involved in viral gene transcription.

SUBMITTER: Kinyanyi D

PROVIDER: S-EPMC5825884 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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<i>In silico</i> structural and functional prediction of African swine fever virus protein-B263R reveals features of a TATA-binding protein.

Kinyanyi Dickson D Obiero George G Obiero George F O GFO Amwayi Peris P Mwaniki Stephen S Wamalwa Mark M

PeerJ 20180222

African swine fever virus (ASFV) is the etiological agent of ASF, a fatal hemorrhagic fever that affects domestic pigs. There is currently no vaccine against ASFV, making it a significant threat to the pork industry. The ASFV genome sequence has been published; however, about half of ASFV open reading frames have not been characterized in terms of their structure and function despite being essential for our understanding of ASFV pathogenicity. The present study reports the three-dimensional stru ...[more]

PMID: 29492339

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Project description:African swine fever virus (ASFV) is a high-consequence pathogen posing a substantial threat to global food security. This large DNA virus encodes more than 150 open reading frames, many of which are uncharacterized. The EP402R gene encodes CD2v, a glycoprotein expressed on the surface of infected cells and the only viral protein known to be present in the virus external envelope. This protein mediates binding of erythrocytes to both cells and virions. This interaction is known to prolong virus persistence in blood thus facilitating viral transmission. The sequence of the extracellular domain of CD2v shows similarity with that of mammalian CD2 proteins and is therefore likely to feature two immunoglobulin (Ig)-like domains. A combination of protein structure modeling and extensive mutagenesis was used to identify residues mediating binding of transiently expressed CD2v to erythrocytes. The N-terminal Ig-like domain AGFCC'C″ β sheet was identified as the putative CD2v erythrocyte-binding area. This region differed from the putative CD58 ligand binding site of host CD2, suggesting that CD2v may bind to a ligand(s) other than CD58. An attenuated genotype I ASFV was constructed by replacing the wild-type EP402R gene for a mutant form expressing CD2v bearing a single amino acid substitution, which abrogated the binding to erythrocytes. Pigs immunized with the recombinant virus developed early antibody and cellular responses, low levels of viremia, mild clinical signs post-immunization, and high levels of protection against challenge. These findings improve our understanding of virus-host interactions and provide a promising approach to modified live vaccine development.ImportanceA better understanding of the interactions between viruses and their hosts is a crucial step in the development of strategies for controlling viral diseases, such as vaccines and antivirals. African swine fever, a pig disease with fatality rates approaching 100%, causes very substantial economic losses in affected countries, and new control measures are clearly needed. In this study, we characterized the interaction between the ASFV CD2v protein and host erythrocytes. The interaction plays a key role in viral persistence in blood since it can allow the virus to "hide" from the host immune system. We identified the amino acids in the viral protein that mediate the interaction with erythrocytes and used this information to construct a mutant virus that is no longer able to bind these cells. This virus induces strong immune responses that provide high levels of protection against infection with the deadly parental virus.

Project description:Recently moderate-virulence classical swine fever virus (CSFV) strains have been proven capable of generating postnatal persistent infection (PI), defined by the maintenance of viremia and the inability to generate CSFV-specific immune responses in animals. These animals also showed a type I interferon blockade in the absence of clinical signs. In this study, we assessed the infection generated in 7-week-old CSFV PI wild boars after infection with the African swine fever virus (ASFV). The wild boars were divided in two groups and were infected with ASFV. Group A comprised boars who were CSFV PI in a subclinical form and Group B comprised pestivirus-free wild boars. Some relevant parameters related to CSFV replication and the immune response of CSFV PI animals were studied. Additionally, serum soluble factors such as IFN-α, TNF-α, IL-6, IL-10, IFN-γ and sCD163 were analysed before and after ASFV infection to assess their role in disease progression.After ASFV infection, only the CSFV PI wild boars showed progressive acute haemorrhagic disease; however, the survival rates following ASFV infection was similar in both experimental groups. Notwithstanding, the CSFV RNA load of CSFV PI animals remained unaltered over the study; likewise, the ASFV DNA load detected after infection was similar between groups. Interestingly, systemic type I FN-α and IL-10 levels in sera were almost undetectable in CSFV PI animals, yet detectable in Group B, while detectable levels of IFN-γ were found in both groups. Finally, the flow cytometry analysis showed an increase in myelomonocytic cells (CD172a+) and a decrease in CD4+ T cells in the PBMCs from CSFV PI animals after ASFV infection.Our results showed that the immune response plays a role in the progression of disease in CSFV subclinically infected wild boars after ASFV infection, and the immune response comprised the systemic type I interferon blockade. ASFV does not produce any interference with CSFV replication, or vice versa. ASFV infection could be a trigger factor for the disease progression in CSFV PI animals, as their survival after ASFV was similar to that of the pestivirus-free ASFV-infected group. This fact suggests a high resistance in CSFV PI animals even against a virus like ASFV; this may mean that there are relevant implications for CSF control in endemic countries. The diagnosis of ASFV and CSFV co-infection in endemic countries cannot be ruled out and need to be studied in greater depth.

Dataset Information

In silico structural and functional prediction of African swine fever virus protein-B263R reveals features of a TATA-binding protein.

Publications

<i>In silico</i> structural and functional prediction of African swine fever virus protein-B263R reveals features of a TATA-binding protein.

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