M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles.
We have demonstrated that the cellular protein M-Sec promotes the transmission of human T-cell leukemia virus type 1 (HTLV-1) in vitro and in vivo. Here, we show how HTLV-1 utilizes M-Sec for its efficient transmission. HTLV-1-infected CD4+ T cells expressed M-Sec at a higher level than uninfected C...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012919 |
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| author | Masateru Hiyoshi Youssef M Eltalkhawy Randa A Abdelnaser Akira Ono Kazuaki Monde Yosuke Maeda Reem M Mahmoud Naofumi Takahashi Yasuyoshi Hatayama Akihide Ryo Satoshi Nozuma Hiroshi Takashima Ryuji Kubota Shinya Suzu |
| author_facet | Masateru Hiyoshi Youssef M Eltalkhawy Randa A Abdelnaser Akira Ono Kazuaki Monde Yosuke Maeda Reem M Mahmoud Naofumi Takahashi Yasuyoshi Hatayama Akihide Ryo Satoshi Nozuma Hiroshi Takashima Ryuji Kubota Shinya Suzu |
| author_sort | Masateru Hiyoshi |
| collection | DOAJ |
| description | We have demonstrated that the cellular protein M-Sec promotes the transmission of human T-cell leukemia virus type 1 (HTLV-1) in vitro and in vivo. Here, we show how HTLV-1 utilizes M-Sec for its efficient transmission. HTLV-1-infected CD4+ T cells expressed M-Sec at a higher level than uninfected CD4+ T cells. The ex vivo culture of the infected cells upregulated the expression of M-Sec, the level of which was sustained for a long time. The viral structural protein Gag is distributed in a punctate pattern in cells. M-Sec promoted the accumulation of large intracellular Gag puncta. This accumulation was dependent on phosphatidylinositol 4,5-bisphosphate (PIP2), since it was lost upon the removal of PIP2 binding motifs in M-Sec or the depletion of cellular PIP2. The viral envelope protein Env co-localized with the large Gag puncta induced by M-Sec. Furthermore, viral particles produced by M-Sec-expressing cells contained a higher amount of Env. Given that M-Sec alters the cellular distribution of PIP2, these results suggest that M-Sec promotes the formation of infectious viral particles through PIP2. Since the expression of M-Sec is mediated by HTLV-1 Tax protein, M-Sec appears to function in a positive feedback loop that ensures efficient HTLV-1 transmission. |
| format | Article |
| id | doaj-art-c4cf0f69098b4be9b70242f99e547b6b |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-c4cf0f69098b4be9b70242f99e547b6b2025-02-12T05:30:41ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101291910.1371/journal.ppat.1012919M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles.Masateru HiyoshiYoussef M EltalkhawyRanda A AbdelnaserAkira OnoKazuaki MondeYosuke MaedaReem M MahmoudNaofumi TakahashiYasuyoshi HatayamaAkihide RyoSatoshi NozumaHiroshi TakashimaRyuji KubotaShinya SuzuWe have demonstrated that the cellular protein M-Sec promotes the transmission of human T-cell leukemia virus type 1 (HTLV-1) in vitro and in vivo. Here, we show how HTLV-1 utilizes M-Sec for its efficient transmission. HTLV-1-infected CD4+ T cells expressed M-Sec at a higher level than uninfected CD4+ T cells. The ex vivo culture of the infected cells upregulated the expression of M-Sec, the level of which was sustained for a long time. The viral structural protein Gag is distributed in a punctate pattern in cells. M-Sec promoted the accumulation of large intracellular Gag puncta. This accumulation was dependent on phosphatidylinositol 4,5-bisphosphate (PIP2), since it was lost upon the removal of PIP2 binding motifs in M-Sec or the depletion of cellular PIP2. The viral envelope protein Env co-localized with the large Gag puncta induced by M-Sec. Furthermore, viral particles produced by M-Sec-expressing cells contained a higher amount of Env. Given that M-Sec alters the cellular distribution of PIP2, these results suggest that M-Sec promotes the formation of infectious viral particles through PIP2. Since the expression of M-Sec is mediated by HTLV-1 Tax protein, M-Sec appears to function in a positive feedback loop that ensures efficient HTLV-1 transmission.https://doi.org/10.1371/journal.ppat.1012919 |
| spellingShingle | Masateru Hiyoshi Youssef M Eltalkhawy Randa A Abdelnaser Akira Ono Kazuaki Monde Yosuke Maeda Reem M Mahmoud Naofumi Takahashi Yasuyoshi Hatayama Akihide Ryo Satoshi Nozuma Hiroshi Takashima Ryuji Kubota Shinya Suzu M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles. PLoS Pathogens |
| title | M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles. |
| title_full | M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles. |
| title_fullStr | M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles. |
| title_full_unstemmed | M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles. |
| title_short | M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles. |
| title_sort | m sec promotes the accumulation of intracellular htlv 1 gag puncta and the incorporation of env into viral particles |
| url | https://doi.org/10.1371/journal.ppat.1012919 |
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