| Title: | Morphogenesis of bullet-shaped rabies virus particles regulated by TSG101 |
| Authors: | Itakura, Yukari Browse this author |
| Tabata, Koshiro Browse this author |
| Saito, Takeshi Browse this author →KAKEN DB |
| Intaruck, Kittiya Browse this author |
| Kawaguchi, Nijiho Browse this author |
| Kishimoto, Mai Browse this author →KAKEN DB |
| Torii, Shiho Browse this author →KAKEN DB |
| Kobayashi, Shintaro Browse this author →KAKEN DB |
| Ito, Naoto Browse this author →KAKEN DB |
| Harada, Michiko Browse this author |
| Inoue, Satoshi Browse this author →KAKEN DB |
| Maeda, Ken Browse this author →KAKEN DB |
| Takada, Ayato Browse this author →KAKEN DB |
| Hall, William W. Browse this author |
| Orba, Yasuko Browse this author →KAKEN DB |
| Sawa, Hirofumi Browse this author →KAKEN DB |
| Sasaki, Michihito Browse this author →KAKEN DB |
| Keywords: | ESCRT |
| L-domain |
| TSG101 |
| Matrix protein |
| Rabies virus |
| Rhabdovirus |
| Issue Date: | 12-Apr-2023 |
| Publisher: | American Society for Microbiology |
| Journal Title: | Journal of virology |
| Volume: | 97 |
| Issue: | 5 |
| Start Page: | e0043823 |
| Publisher DOI: | 10.1128/jvi.00438-23 |
| PMID: | 37042780 |
| Abstract: | Viral protein assembly and virion budding are tightly regulated to enable the proper formation of progeny virions. At this late stage in the virus life cycle, some enveloped viruses take advantage of the host endosomal sorting complex required for transport (ESCRT) machinery, which contributes to the physiological functions of membrane modulation and abscission. Bullet-shaped viral particles are unique morphological characteristics of rhabdoviruses; however, the involvement of host factors in rhabdovirus infection and, specifically, the molecular mechanisms underlying virion formation are not fully understood. In the present study, we used a small interfering RNA (siRNA) screening approach and found that the ESCRT-I component TSG101 contributes to the propagation of rabies virus (RABV). We demonstrated that the matrix protein (M) of RABV interacts with TSG101 via the late domain containing the PY and YL motifs, which are conserved in various viral proteins. Loss of the YL motif in the RABV M or the downregulation of host TSG101 expression resulted in the intracellular aggregation of viral proteins and abnormal virus particle formation, indicating a defect in the RABV assembly and budding processes. These results indicate that the interaction of the RABV M and TSG101 is pivotal for not only the efficient budding of progeny RABV from infected cells but also for the bullet-shaped virion morphology.
IMPORTANCE Enveloped viruses bud from cells with the host lipid bilayer. Generally, the membrane modulation and abscission are mediated by host ESCRT complexes. Some enveloped viruses utilize their late (L-) domain to interact with ESCRTs, which promotes viral budding. Rhabdoviruses form characteristic bullet-shaped enveloped virions, but the underlying molecular mechanisms involved remain elusive. Here, we showed that TSG101, one of the ESCRT components, supports rabies virus (RABV) budding and proliferation. TSG101 interacted with RABV matrix protein via the L-domain, and the absence of this interaction resulted in intracellular virion accumulation and distortion of the morphology of progeny virions. Our study reveals that virion formation of RABV is highly regulated by TSG101 and the virus matrix protein. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/89814 |
| Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
