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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Host Retromer Protein Sorting Nexin 2 Interacts with Human Respiratory Syncytial Virus Structural Proteins and is Required for Efficient Viral Production

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Autor(es):
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Cardoso, Ricardo S. [1] ; Tavares, Lucas Alves [1] ; Jesus, Bruna Lais S. [1] ; Criado, Miria F. [1] ; de Carvalho, Andreia Nogueira [1] ; Souza, Juliano de Paula [1] ; Bedi, Sukhmani [2] ; de Souza, Marcos Michel [1] ; Silva, Maria Lucia [1] ; Lanfredi, Guilherme Pauperio [3] ; Vitti, Brenda Cristina [1] ; Scudero, Orlando Bonito [4] ; Faca, Vitor Marcel [3] ; Ono, Akira [2] ; Ventura, Armando M. [4] ; DaSilva, Luis Lamberti P. [1] ; Arruda, Eurico [1]
Número total de Autores: 17
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Dept Cell & Mol Biol, Ribeirao Preto - Brazil
[2] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 - USA
[3] Univ Sao Paulo, Dept Biochem, Sch Med, Ribeirao Preto - Brazil
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: MBIO; v. 11, n. 5 SEP-OCT 2020.
Citações Web of Science: 0
Resumo

Human respiratory syncytial virus (HRSV) envelope glycoproteins traffic to assembly sites through the secretory pathway, while nonglycosylated proteins M and N are present in HRSV inclusion bodies but must reach the plasma membrane, where HRSV assembly happens. Little is known about how nonglycosylated HRSV proteins reach assembly sites. Here, we show that HRSV M and N proteins partially colocalize with the Golgi marker giantin, and the glycosylated F and nonglycosylated N proteins are closely located in the trans-Golgi, suggesting their interaction in that compartment. Brefeldin A compromised the trafficking of HRSV F and N proteins and inclusion body sizes, indicating that the Golgi is important for both glycosylated and nonglycosylated HRSV protein traffic. HRSV N and M proteins colocalized and interacted with sorting nexin 2 (SNX2), a retromer component that shapes endosomes in tubular structures. Glycosylated F and nonglycosylated N HRSV proteins are detected in SNX2-laden aggregates with intracellular filaments projecting from their outer surfaces, and VPS26, another retromer component, was also found in inclusion bodies and filament-shaped structures. Similar to SNX2, TGN46 also colocalized with HRSV M and N proteins in filamentous structures at the plasma membrane. Cell fractionation showed enrichment of SNX2 in fractions containing HRSV M and N proteins. Silencing of SNX1 and 2 was associated with reduction in viral proteins, HRSV inclusion body size, syncytium formation, and progeny production. The results indicate that HRSV structural proteins M and N are in the secretory pathway, and SNX2 plays an important role in the traffic of HRSV structural proteins toward assembly sites. IMPORTANCE The present study contributes new knowledge to understand HRSV assembly by providing evidence that nonglycosylated structural proteins M and N interact with elements of the secretory pathway, shedding light on their intracellular traffic. To the best of our knowledge, the present contribution is important given the scarcity of studies about the traffic of HRSV nonglycosylated proteins, especially by pointing to the involvement of SNX2, a retromer component, in the HRSV assembly process. (AU)

Processo FAPESP: 13/16349-2 - Estudos sobre infecções persistentes por Paramyxovirus respiratórios humanos
Beneficiário:Eurico de Arruda Neto
Modalidade de apoio: Auxílio à Pesquisa - Regular