The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replication
ABSTRACT Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a nee...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2024-01-01
|
| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02609-23 |
| _version_ | 1797357388147195904 |
|---|---|
| author | Sonja C. J. H. Chua Jianzhou Cui Karishma Sachaphibulkij Isabelle Siang Ling Tan Hui Qing Tan Hong Meng Lim David Engelberg Lina H. K. Lim |
| author_facet | Sonja C. J. H. Chua Jianzhou Cui Karishma Sachaphibulkij Isabelle Siang Ling Tan Hui Qing Tan Hong Meng Lim David Engelberg Lina H. K. Lim |
| author_sort | Sonja C. J. H. Chua |
| collection | DOAJ |
| description | ABSTRACT Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a need for host-targeted therapies against influenza to provide an effective alternative therapeutic target. Sec13 was identified as a novel host interactor of influenza. As Sec13 is a member of the nuclear pore complex and coat protein complex II (COPII) vesicles, localization of both Sec13 and non-structural protein 1 (NS1) in the nucleus, endoplasmic reticulum (ER), COPII vesicles (ER-to-Golgi transport), and Golgi was studied during infection. Sec13 is associated with ER, COPII, and Golgi in infected lung epithelial cells and not the nucleus during PR8 infection. This observation would imply the functional role of Sec13 in the COPII vesicles (ER-to-Golgi transport). Moreover, the colocalization of NS1 and Sec13 were correlated at several time points of infection, indicating the function of Sec13 during influenza infection. Inhibiting the ER-to-Golgi transport and silencing Sec13 decreased viral titers, whereas overexpressing Sec13 increased viral titers. Hence, we propose that the ER-to-Golgi transport is an important pathway of viral replication and viral export, and specifically, Sec13 has a functional role in influenza replication and virulence. IMPORTANCE Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a need for host-targeted therapies against influenza to provide an effective alternative therapeutic target. Sec13 was identified as a novel host interactor of influenza. Endoplasmic reticulum-to-Golgi transport is an important pathway of influenza virus replication and viral export. Specifically, Sec13 has a functional role in influenza replication and virulence. |
| first_indexed | 2024-03-08T14:44:24Z |
| format | Article |
| id | doaj.art-da3b4fb358054634ad3e30135eb6c9a3 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-08T14:44:24Z |
| publishDate | 2024-01-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-da3b4fb358054634ad3e30135eb6c9a32024-01-11T14:04:37ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972024-01-0112110.1128/spectrum.02609-23The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replicationSonja C. J. H. Chua0Jianzhou Cui1Karishma Sachaphibulkij2Isabelle Siang Ling Tan3Hui Qing Tan4Hong Meng Lim5David Engelberg6Lina H. K. Lim7Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, SingaporeCREATE-NUS-HUJ Molecular Mechanisms of Inflammatory Diseases Programme, National University of Singapore , Singapore, SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, SingaporeABSTRACT Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a need for host-targeted therapies against influenza to provide an effective alternative therapeutic target. Sec13 was identified as a novel host interactor of influenza. As Sec13 is a member of the nuclear pore complex and coat protein complex II (COPII) vesicles, localization of both Sec13 and non-structural protein 1 (NS1) in the nucleus, endoplasmic reticulum (ER), COPII vesicles (ER-to-Golgi transport), and Golgi was studied during infection. Sec13 is associated with ER, COPII, and Golgi in infected lung epithelial cells and not the nucleus during PR8 infection. This observation would imply the functional role of Sec13 in the COPII vesicles (ER-to-Golgi transport). Moreover, the colocalization of NS1 and Sec13 were correlated at several time points of infection, indicating the function of Sec13 during influenza infection. Inhibiting the ER-to-Golgi transport and silencing Sec13 decreased viral titers, whereas overexpressing Sec13 increased viral titers. Hence, we propose that the ER-to-Golgi transport is an important pathway of viral replication and viral export, and specifically, Sec13 has a functional role in influenza replication and virulence. IMPORTANCE Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a need for host-targeted therapies against influenza to provide an effective alternative therapeutic target. Sec13 was identified as a novel host interactor of influenza. Endoplasmic reticulum-to-Golgi transport is an important pathway of influenza virus replication and viral export. Specifically, Sec13 has a functional role in influenza replication and virulence.https://journals.asm.org/doi/10.1128/spectrum.02609-23influenzaH1N1H3N2non-structural protein 1 (NS1)Sec13COPII |
| spellingShingle | Sonja C. J. H. Chua Jianzhou Cui Karishma Sachaphibulkij Isabelle Siang Ling Tan Hui Qing Tan Hong Meng Lim David Engelberg Lina H. K. Lim The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replication Microbiology Spectrum influenza H1N1 H3N2 non-structural protein 1 (NS1) Sec13 COPII |
| title | The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replication |
| title_full | The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replication |
| title_fullStr | The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replication |
| title_full_unstemmed | The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replication |
| title_short | The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replication |
| title_sort | er golgi transport of influenza virus through ns1 sec13 association during virus replication |
| topic | influenza H1N1 H3N2 non-structural protein 1 (NS1) Sec13 COPII |
| url | https://journals.asm.org/doi/10.1128/spectrum.02609-23 |
| work_keys_str_mv | AT sonjacjhchua theergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT jianzhoucui theergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT karishmasachaphibulkij theergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT isabellesianglingtan theergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT huiqingtan theergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT hongmenglim theergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT davidengelberg theergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT linahklim theergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT sonjacjhchua ergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT jianzhoucui ergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT karishmasachaphibulkij ergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT isabellesianglingtan ergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT huiqingtan ergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT hongmenglim ergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT davidengelberg ergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication AT linahklim ergolgitransportofinfluenzavirusthroughns1sec13associationduringvirusreplication |