The RING domain and the L79 residue of Z protein are involved in both the rescue of nucleocapsids and the incorporation of glycoproteins into infectious chimeric arenavirus-like particles

Arenaviruses, such as Tacaribe virus (TacV) and its closely related pathogenic Junin virus (JunV), are enveloped viruses with a bipartite negative-sense RNA genome that encodes the nucleocapsid protein (N), the precursor of the envelope glycoprotein complex (GP), the polymerase (L), and a RING finge...

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Detalhes bibliográficos
Autores: Casabona, Juan Cruz, Levingston Macleod, Jesica M., Loureiro, Maria Eugenia, Gomez, Guillermo Alberto, Lopez, Nora Mabel
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2009
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositório:CONICET Digital (CONICET)
Idioma:inglês
OAI Identifier:oai:ri.conicet.gov.ar:11336/98065
Acesso em linha:http://hdl.handle.net/11336/98065
Access Level:Acceso aberto
Palavra-chave:Arenavirus
Z protein
assembly
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descrição
Resumo:Arenaviruses, such as Tacaribe virus (TacV) and its closely related pathogenic Junin virus (JunV), are enveloped viruses with a bipartite negative-sense RNA genome that encodes the nucleocapsid protein (N), the precursor of the envelope glycoprotein complex (GP), the polymerase (L), and a RING finger protein (Z), which is the driving force of arenavirus budding. We have established a plasmid-based system which allowed the successful packaging of TacV-like nucleocapsids along with Z and GP of JunV into infectious virus-like particles (VLPs). By coexpressing different combinations of the system components, followed by biochemical analysis of the VLPs, the requirements for the assembly of both N and GP into particles were defined. We found that coexpression of N with Z protein in the absence of minigenome and other viral proteins was sufficient to recruit N within lipid-enveloped Z-containing VLPs. In addition, whereas GP was not required for the incorporation of N, coexpression of N substantially enhanced the ratio of GP to Z into VLPs. Disruption of the RING structure or mutation of residue L79 to alanine within Z protein, although it had no effect on Z self-budding, severely impaired VLP infectivity. These mutations drastically altered intracellular Z-N interactions and the incorporation of both N and GP into VLPs. Our results support the conclusion that the interaction between Z and N is required for assembly of both the nucleocapsids and the glycoproteins into infectious arenavirus budding particles.