| Autor: |
Jäger N; Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany.; Faculty of Biology and Psychology, Georg-August-University Göttingen, 37073 Göttingen, Germany., Ayyub SA; Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany., Korniy N; Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany., Peske F; Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany., Hoffmann M; Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany.; Faculty of Biology and Psychology, Georg-August-University Göttingen, 37073 Göttingen, Germany., Rodnina MV; Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany., Pöhlmann S; Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany.; Faculty of Biology and Psychology, Georg-August-University Göttingen, 37073 Göttingen, Germany. |
| Abstrakt: |
The interferon-induced host cell protein shiftless (SFL) was reported to inhibit human immunodeficiency virus (HIV) infection by blocking the -1 programmed ribosomal frameshifting (-1PRF) required for expression of the Gag-Pol polyprotein. However, it is not clear how SFL inhibits -1PRF. To address this question, we focused on a 36 amino acids comprising region (termed required for antiviral activity (RAA)) that is essential for suppression of -1PRF and HIV infection and is missing from SFL short (SFLS), a splice variant of SFL with unknown function. Here, we confirm that SFL, but not SFLS, inhibits HIV -1PRF and show that inhibition is cell-type-independent. Mutagenic and biochemical analyses demonstrated that the RAA region is required for SFL self-interactions and confirmed that it is necessary for ribosome association and binding to the HIV RNA. Analysis of SFL mutants with six consecutive amino-acids-comprising deletions in the RAA region suggests effects on binding to the HIV RNA, complete inhibition of -1PRF, inhibition of Gag-Pol expression, and antiviral activity. In contrast, these amino acids did not affect SFL expression and were partially dispensable for SFL self-interactions and binding to the ribosome. Collectively, our results support the notion that SFL binds to the ribosome and the HIV RNA in order to block -1PRF and HIV infection, and suggest that the multimerization of SFL may be functionally important. |
