Host Retromer Protein Sorting Nexin 2 Interacts with Human Respiratory Syncytial Virus Structural Proteins and is Required for Efficient Viral Production
ABSTRACT 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 non...
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American Society for Microbiology
2020
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oai:doaj.org-article:677e053382274242a051b92585a6cb7e2021-11-15T16:19:07ZHost Retromer Protein Sorting Nexin 2 Interacts with Human Respiratory Syncytial Virus Structural Proteins and is Required for Efficient Viral Production10.1128/mBio.01869-202150-7511https://doaj.org/article/677e053382274242a051b92585a6cb7e2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01869-20https://doaj.org/toc/2150-7511ABSTRACT 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.Ricardo S. CardosoLucas Alves TavaresBruna Lais S. JesusMiria F. CriadoAndreia Nogueira de CarvalhoJuliano de Paula SouzaSukhmani BediMarcos Michel de SouzaMaria Lucia SilvaGuilherme Pauperio LanfrediBrenda Cristina VittiOrlando Bonito ScuderoVitor Marcel FaçaAkira OnoArmando M. VenturaLuis Lamberti P. daSilvaEurico ArrudaAmerican Society for Microbiologyarticlehuman respiratory syncytial virusparamyxovirusprotein traffickingvirus-host interactionsMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020) |
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| collection |
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| language |
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| topic |
human respiratory syncytial virus paramyxovirus protein trafficking virus-host interactions Microbiology QR1-502 |
| spellingShingle |
human respiratory syncytial virus paramyxovirus protein trafficking virus-host interactions Microbiology QR1-502 Ricardo S. Cardoso Lucas Alves Tavares Bruna Lais S. Jesus Miria F. Criado Andreia Nogueira de Carvalho Juliano de Paula Souza Sukhmani Bedi Marcos Michel de Souza Maria Lucia Silva Guilherme Pauperio Lanfredi Brenda Cristina Vitti Orlando Bonito Scudero Vitor Marcel Faça Akira Ono Armando M. Ventura Luis Lamberti P. daSilva Eurico Arruda Host Retromer Protein Sorting Nexin 2 Interacts with Human Respiratory Syncytial Virus Structural Proteins and is Required for Efficient Viral Production |
| description |
ABSTRACT 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. |
| format |
article |
| author |
Ricardo S. Cardoso Lucas Alves Tavares Bruna Lais S. Jesus Miria F. Criado Andreia Nogueira de Carvalho Juliano de Paula Souza Sukhmani Bedi Marcos Michel de Souza Maria Lucia Silva Guilherme Pauperio Lanfredi Brenda Cristina Vitti Orlando Bonito Scudero Vitor Marcel Faça Akira Ono Armando M. Ventura Luis Lamberti P. daSilva Eurico Arruda |
| author_facet |
Ricardo S. Cardoso Lucas Alves Tavares Bruna Lais S. Jesus Miria F. Criado Andreia Nogueira de Carvalho Juliano de Paula Souza Sukhmani Bedi Marcos Michel de Souza Maria Lucia Silva Guilherme Pauperio Lanfredi Brenda Cristina Vitti Orlando Bonito Scudero Vitor Marcel Faça Akira Ono Armando M. Ventura Luis Lamberti P. daSilva Eurico Arruda |
| author_sort |
Ricardo S. Cardoso |
| title |
Host Retromer Protein Sorting Nexin 2 Interacts with Human Respiratory Syncytial Virus Structural Proteins and is Required for Efficient Viral Production |
| title_short |
Host Retromer Protein Sorting Nexin 2 Interacts with Human Respiratory Syncytial Virus Structural Proteins and is Required for Efficient Viral Production |
| title_full |
Host Retromer Protein Sorting Nexin 2 Interacts with Human Respiratory Syncytial Virus Structural Proteins and is Required for Efficient Viral Production |
| title_fullStr |
Host Retromer Protein Sorting Nexin 2 Interacts with Human Respiratory Syncytial Virus Structural Proteins and is Required for Efficient Viral Production |
| title_full_unstemmed |
Host Retromer Protein Sorting Nexin 2 Interacts with Human Respiratory Syncytial Virus Structural Proteins and is Required for Efficient Viral Production |
| title_sort |
host retromer protein sorting nexin 2 interacts with human respiratory syncytial virus structural proteins and is required for efficient viral production |
| publisher |
American Society for Microbiology |
| publishDate |
2020 |
| url |
https://doaj.org/article/677e053382274242a051b92585a6cb7e |
| work_keys_str_mv |
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