ARHGAP1 Transported with Influenza Viral Genome Ensures Integrity of Viral Particle Surface through Efficient Budozone Formation
ABSTRACT Influenza viral particles are assembled at the plasma membrane concomitantly with Rab11a-mediated endocytic transport of viral ribonucleoprotein complexes (vRNPs). The mechanism of spatiotemporal regulation of viral budozone formation and its regulatory molecules on the endocytic vesicles r...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-06-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.00721-22 |
| _version_ | 1811237388390760448 |
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| author | Takahiro Kuroki Tomohisa Hatta Tohru Natsume Nobuaki Sakai Akira Yagi Kohsuke Kato Kyosuke Nagata Atsushi Kawaguchi |
| author_facet | Takahiro Kuroki Tomohisa Hatta Tohru Natsume Nobuaki Sakai Akira Yagi Kohsuke Kato Kyosuke Nagata Atsushi Kawaguchi |
| author_sort | Takahiro Kuroki |
| collection | DOAJ |
| description | ABSTRACT Influenza viral particles are assembled at the plasma membrane concomitantly with Rab11a-mediated endocytic transport of viral ribonucleoprotein complexes (vRNPs). The mechanism of spatiotemporal regulation of viral budozone formation and its regulatory molecules on the endocytic vesicles remain unclear. Here, we performed a proximity-based proteomics approach for Rab11a and found that ARHGAP1, a Rho GTPase-activating protein, is transported through the Rab11a-mediated apical transport of vRNP. ARHGAP1 stabilized actin filaments in infected cells for the lateral clustering of hemagglutinin (HA) molecules, a viral surface membrane protein, to the budozone. Disruption of the HA clustering results in the production of virions with low HA content, and such virions were less resistant to protease and had enhanced antigenicity, presumably because reduced clustering of viral membrane proteins exposes hidden surfaces. Collectively, these results demonstrate that Rab11a-mediated endocytic transport of ARHGAP1 with vRNPs stimulates budozone formation to ensure the integrity of virion surface required for viral survival. IMPORTANCE The endocytic transport of the influenza viral genome triggers the clustering of viral membrane proteins at the plasma membrane to form the viral budozone. However, host factors that promote viral budozone formation in concert with viral genome transport have not been identified. Here, we found that ARHGAP1, a negative regulator of the Rho family protein, is transported with the viral genome and stabilizes actin filaments to promote budozone formation. We have shown that ARHGAP1-mediated efficient formation of viral budozone was crucial for the clustering of viral HA protein to the progeny viral particles. The clustering of HA proteins on the virions is responsible for the structural integrity of the viral particles, which promotes viral stability and viral immune evasion. This study highlights the molecular mechanism that works in concert with viral genome packaging to ensure the structural integrity of viral particles. |
| first_indexed | 2024-04-12T12:23:33Z |
| format | Article |
| id | doaj.art-c288769fe7c848cabf3b9a07096b6c58 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-12T12:23:33Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-c288769fe7c848cabf3b9a07096b6c582022-12-22T03:33:14ZengAmerican Society for MicrobiologymBio2150-75112022-06-0113310.1128/mbio.00721-22ARHGAP1 Transported with Influenza Viral Genome Ensures Integrity of Viral Particle Surface through Efficient Budozone FormationTakahiro Kuroki0Tomohisa Hatta1Tohru Natsume2Nobuaki Sakai3Akira Yagi4Kohsuke Kato5Kyosuke Nagata6Atsushi Kawaguchi7Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, JapanRobotic Biology Institute Inc., Tokyo, JapanRobotic Biology Institute Inc., Tokyo, JapanDepartment of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanR&D Group, Olympus Corporation, Hachioji, JapanGraduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, JapanDepartment of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanGraduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, JapanABSTRACT Influenza viral particles are assembled at the plasma membrane concomitantly with Rab11a-mediated endocytic transport of viral ribonucleoprotein complexes (vRNPs). The mechanism of spatiotemporal regulation of viral budozone formation and its regulatory molecules on the endocytic vesicles remain unclear. Here, we performed a proximity-based proteomics approach for Rab11a and found that ARHGAP1, a Rho GTPase-activating protein, is transported through the Rab11a-mediated apical transport of vRNP. ARHGAP1 stabilized actin filaments in infected cells for the lateral clustering of hemagglutinin (HA) molecules, a viral surface membrane protein, to the budozone. Disruption of the HA clustering results in the production of virions with low HA content, and such virions were less resistant to protease and had enhanced antigenicity, presumably because reduced clustering of viral membrane proteins exposes hidden surfaces. Collectively, these results demonstrate that Rab11a-mediated endocytic transport of ARHGAP1 with vRNPs stimulates budozone formation to ensure the integrity of virion surface required for viral survival. IMPORTANCE The endocytic transport of the influenza viral genome triggers the clustering of viral membrane proteins at the plasma membrane to form the viral budozone. However, host factors that promote viral budozone formation in concert with viral genome transport have not been identified. Here, we found that ARHGAP1, a negative regulator of the Rho family protein, is transported with the viral genome and stabilizes actin filaments to promote budozone formation. We have shown that ARHGAP1-mediated efficient formation of viral budozone was crucial for the clustering of viral HA protein to the progeny viral particles. The clustering of HA proteins on the virions is responsible for the structural integrity of the viral particles, which promotes viral stability and viral immune evasion. This study highlights the molecular mechanism that works in concert with viral genome packaging to ensure the structural integrity of viral particles.https://journals.asm.org/doi/10.1128/mbio.00721-22actin filamentinfluenza virusrecycling endosomeviral assembly |
| spellingShingle | Takahiro Kuroki Tomohisa Hatta Tohru Natsume Nobuaki Sakai Akira Yagi Kohsuke Kato Kyosuke Nagata Atsushi Kawaguchi ARHGAP1 Transported with Influenza Viral Genome Ensures Integrity of Viral Particle Surface through Efficient Budozone Formation mBio actin filament influenza virus recycling endosome viral assembly |
| title | ARHGAP1 Transported with Influenza Viral Genome Ensures Integrity of Viral Particle Surface through Efficient Budozone Formation |
| title_full | ARHGAP1 Transported with Influenza Viral Genome Ensures Integrity of Viral Particle Surface through Efficient Budozone Formation |
| title_fullStr | ARHGAP1 Transported with Influenza Viral Genome Ensures Integrity of Viral Particle Surface through Efficient Budozone Formation |
| title_full_unstemmed | ARHGAP1 Transported with Influenza Viral Genome Ensures Integrity of Viral Particle Surface through Efficient Budozone Formation |
| title_short | ARHGAP1 Transported with Influenza Viral Genome Ensures Integrity of Viral Particle Surface through Efficient Budozone Formation |
| title_sort | arhgap1 transported with influenza viral genome ensures integrity of viral particle surface through efficient budozone formation |
| topic | actin filament influenza virus recycling endosome viral assembly |
| url | https://journals.asm.org/doi/10.1128/mbio.00721-22 |
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