Role of Capsid anchor in the morphogenesis of Zika virus
The flavivirus capsid protein (C) is separated from the downstream pre-membrane (PrM) protein by a hydrophobic sequence named capsid anchor (Ca). During polyprotein processing, Ca is sequentially cleaved by the viral NS2B/NS3 protease on the cytosolic side and by signal peptidase on the luminal side...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Microbiology
2018
|
| _version_ | 1826263723741806592 |
|---|---|
| author | Rana, J Slon Campos, J Leccese, G Francolini, M Bestagno, M Poggianella, M Burrone, O |
| author_facet | Rana, J Slon Campos, J Leccese, G Francolini, M Bestagno, M Poggianella, M Burrone, O |
| author_sort | Rana, J |
| collection | OXFORD |
| description | The flavivirus capsid protein (C) is separated from the downstream pre-membrane (PrM) protein by a hydrophobic sequence named capsid anchor (Ca). During polyprotein processing, Ca is sequentially cleaved by the viral NS2B/NS3 protease on the cytosolic side and by signal peptidase on the luminal side of the ER. To date, Ca is considered important mostly for directing translocation of PrM into the ER lumen. In this study, the role of Ca in the assembly and secretion of ZIKV was investigated using a pseudovirus-based approach. Our results show that, while Ca-mediated anchoring of C to the ER membrane is not needed for the production of infective particles, Ca expression in cis with respect to PrM is strictly required to allow proper assembly of infectious particles. Finally, we show that the presence of a heterologous, but not the homologous, Ca induces degradation of E through the autophagy/lysosomal pathway.IMPORTANCE The capsid anchor (Ca) is a single pass transmembrane domain at the C-terminus of the capsid protein (C) known to function as a signal for the translocation of PrM into the ER lumen. The objective of this study was to further understand the role of Ca in ZIKV life cycle, whether involved in the formation of nucleocapsid through association with C or in the formation of viral envelope. In this study, we show that Ca has a function beyond the one of translocation signal, controlling protein E stability and therefore its availability for assembly of infectious particles. |
| first_indexed | 2024-03-06T19:56:21Z |
| format | Journal article |
| id | oxford-uuid:25bcb822-b7ff-4e7a-9519-f4714cacfb2a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:56:21Z |
| publishDate | 2018 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:25bcb822-b7ff-4e7a-9519-f4714cacfb2a2022-03-26T11:57:09ZRole of Capsid anchor in the morphogenesis of Zika virusJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:25bcb822-b7ff-4e7a-9519-f4714cacfb2aEnglishSymplectic Elements at OxfordAmerican Society for Microbiology2018Rana, JSlon Campos, JLeccese, GFrancolini, MBestagno, MPoggianella, MBurrone, OThe flavivirus capsid protein (C) is separated from the downstream pre-membrane (PrM) protein by a hydrophobic sequence named capsid anchor (Ca). During polyprotein processing, Ca is sequentially cleaved by the viral NS2B/NS3 protease on the cytosolic side and by signal peptidase on the luminal side of the ER. To date, Ca is considered important mostly for directing translocation of PrM into the ER lumen. In this study, the role of Ca in the assembly and secretion of ZIKV was investigated using a pseudovirus-based approach. Our results show that, while Ca-mediated anchoring of C to the ER membrane is not needed for the production of infective particles, Ca expression in cis with respect to PrM is strictly required to allow proper assembly of infectious particles. Finally, we show that the presence of a heterologous, but not the homologous, Ca induces degradation of E through the autophagy/lysosomal pathway.IMPORTANCE The capsid anchor (Ca) is a single pass transmembrane domain at the C-terminus of the capsid protein (C) known to function as a signal for the translocation of PrM into the ER lumen. The objective of this study was to further understand the role of Ca in ZIKV life cycle, whether involved in the formation of nucleocapsid through association with C or in the formation of viral envelope. In this study, we show that Ca has a function beyond the one of translocation signal, controlling protein E stability and therefore its availability for assembly of infectious particles. |
| spellingShingle | Rana, J Slon Campos, J Leccese, G Francolini, M Bestagno, M Poggianella, M Burrone, O Role of Capsid anchor in the morphogenesis of Zika virus |
| title | Role of Capsid anchor in the morphogenesis of Zika virus |
| title_full | Role of Capsid anchor in the morphogenesis of Zika virus |
| title_fullStr | Role of Capsid anchor in the morphogenesis of Zika virus |
| title_full_unstemmed | Role of Capsid anchor in the morphogenesis of Zika virus |
| title_short | Role of Capsid anchor in the morphogenesis of Zika virus |
| title_sort | role of capsid anchor in the morphogenesis of zika virus |
| work_keys_str_mv | AT ranaj roleofcapsidanchorinthemorphogenesisofzikavirus AT sloncamposj roleofcapsidanchorinthemorphogenesisofzikavirus AT lecceseg roleofcapsidanchorinthemorphogenesisofzikavirus AT francolinim roleofcapsidanchorinthemorphogenesisofzikavirus AT bestagnom roleofcapsidanchorinthemorphogenesisofzikavirus AT poggianellam roleofcapsidanchorinthemorphogenesisofzikavirus AT burroneo roleofcapsidanchorinthemorphogenesisofzikavirus |