N4BP1 restricts HIV-1 and its inactivation by MALT1 promotes viral reactivation
| Autor: | Yamasoba, Daichi, Sato, Kei, Ichinose, Takuya, Imamura, Tomoko, Koepke, Lennart, Joas, Simone, Reith, Elisabeth, Hotter, Dominik, Misawa, Naoko, Akaki, Kotaro, Uehata, Takuya, Mino, Takashi, Miyamoto, Sho, Noda, Takeshi, Yamashita, Akio, Standley, Daron M., Kirchhoff, Frank, Sauter, Daniel, Koyanagi, Yoshio, Takeuchi, Osamu |
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| Rok vydání: | 2018 |
| Předmět: |
CD4-Positive T-Lymphocytes
Macrophages Receptors Antigen T-Cell Gene Expression Interferon-alpha Nuclear Proteins RNA-Binding Proteins HIV Infections RNA decay Cell Line Virus Latency Mice Protein Domains Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein HIV-1 Animals Humans RNA Viral Virus Activation Restriction factors RNA Messenger |
| Zdroj: | Nature microbiology. 4(9) |
| ISSN: | 2058-5276 |
| Popis: | RNA-modulating factors not only regulate multiple steps of cellular RNA metabolism, but also emerge as key effectors of the immune response against invading viral pathogens including human immunodeficiency virus type-1 (HIV-1). However, the cellular RNA-binding proteins involved in the establishment and maintenance of latent HIV-1 reservoirs have not been extensively studied. Here, we screened a panel of 62 cellular RNA-binding proteins and identified NEDD4-binding protein 1 (N4BP1) as a potent interferon-inducible inhibitor of HIV-1 in primary T cells and macrophages. N4BP1 harbours a prototypical PilT N terminus-like RNase domain and inhibits HIV-1 replication by interacting with and degrading viral mRNA species. Following activation of CD4+ T cells, however, N4BP1 undergoes rapid cleavage at Arg 509 by the paracaspase named mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1). Mutational analyses and knockout studies revealed that MALT1-mediated inactivation of N4BP1 facilitates the reactivation of latent HIV-1 proviruses. Taken together, our findings demonstrate that the RNase N4BP1 is an efficient restriction factor of HIV-1 and suggest that inactivation of N4BP1 by induction of MALT1 activation might facilitate elimination of latent HIV-1 reservoirs. 宿主がHIV-1感染を抑制する新たなメカニズムの解明 --N4BP1によるRNA分解とその調節がウイルス再活性化を調節する--. 京都大学プレスリリース. 2019-05-29. |
| Databáze: | OpenAIRE |
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