Detalhes do Documento

In vitro and in silico studies reveal capsid-mutant Porcine circovirus 2b with novel cytopathogenic and structural characteristics

Autor(es): Cruz, Taís Fukuta [UNESP] ; Magro, Angelo José [UNESP] ; de Castro, Alessandra M.M.G. ; Pedraza-Ordoñez, Francisco J. ; Tsunemi, Miriam Harumi [UNESP] ; Perahia, David ; Araujo, João Pessoa [UNESP]

Data: 2018

Identificador Persistente: http://hdl.handle.net/11449/176303

Origem: Oasisbr

Assunto(s): Amino acid mutations; Cap protein; Molecular modeling; PCV2b mutants; Porcine circovirus; Viral replication


Descrição

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Porcine circovirus 2 (PCV2) is an icosahedral, non-enveloped, and single-stranded circular DNA virus that belongs to the family Circoviridae, genus Circovirus, and is responsible for a complex of different diseases defined as porcine circovirus diseases (PCVDs). These diseases – including postweaning multisystemic wasting syndrome (PMWS), enteric disease, respiratory disease, porcine dermatitis and nephropathy syndrome (PDNS), and reproductive failure – are responsible for large economic losses in the pig industry. After serial passages in swine testicle (ST) cells of a wild-type virus isolated from an animal with PMWS, we identified three PCV2b viruses with capsid protein (known as Cap protein) cumulative mutations, including two novel mutants. The mutant viruses were introduced into new ST cell cultures for reisolation and showed, in comparison to the wild-type PCV2b, remarkable viral replication efficiency (> 1011 DNA copies/ml) and cell death via necrosis, which were clearly related to the accretion of capsid protein mutations. The analysis of a Cap protein/capsid model showed that the mutated residues were located in solvent-accessible positions on the external PCV2b surface. Additionally, the mutated residues were found in linear epitopes and participated in pockets on the capsid surface, indicating that these residues could also be involved in antibody recognition. Taking into account the likely natural emergence of PCV2b variants, it is possible to consider that the results of this work increase knowledge of Circovirus biology and could help to prevent future serious cases of vaccine failure that could lead to heavy losses to the swine industry.

Departamento de Microbiologia e Imunologia Instituto de Biociências (IB) Universidade Estadual Paulista (Unesp)

Instituto de Biotecnologia (IBTEC) Universidade Estadual Paulista (Unesp)

Departamento de Bioprocessos e Biotecnologia Faculdade de Ciências Agronômicas (FCA) Universidade Estadual Paulista (Unesp)

Departamento de Medicina Veterinária Preventiva e Saúde Animal Universidade de São Paulo (USP)

Departamento de Salud Animal Universidad de Caldas

Departamento de Bioestatística Instituto de Biociências (IB) Universidade Estadual Paulista (Unesp)

Laboratoire de Biologie et de Pharmacologie Appliquée ENS Cachan/Université Paris-Saclay

Complexo Educacional Faculdades Metropolitanas Unidas (FMU/HOVET) São Paulo São Paulo

Departamento de Microbiologia e Imunologia Instituto de Biociências (IB) Universidade Estadual Paulista (Unesp)

Instituto de Biotecnologia (IBTEC) Universidade Estadual Paulista (Unesp)

Departamento de Bioprocessos e Biotecnologia Faculdade de Ciências Agronômicas (FCA) Universidade Estadual Paulista (Unesp)

Departamento de Bioestatística Instituto de Biociências (IB) Universidade Estadual Paulista (Unesp)

FAPESP: 2006/57976-6

FAPESP: 2006/59002-9

FAPESP: 2013/14530-1

Tipo de Documento Artigo científico
Idioma Inglês
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