Academic Journal
Regulation of HIV-2 Vpx/Vpr expression by the poly-proline motif: Enhancement of protein dimerization and translation.
| Τίτλος: | Regulation of HIV-2 Vpx/Vpr expression by the poly-proline motif: Enhancement of protein dimerization and translation. |
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| Συγγραφείς: | Nakamura Y; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Ahagon-Edamura A; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Koga R; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Shimagaki K; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Uesugi M; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Fujino H; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Beyri B; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Arakaki Y; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Ciftci H; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan; Department of Molecular Biology and Genetics, Burdur Mehmet Akif Ersoy University, Burdur, 15200, Turkey; Research and Development, Science Farm Ltd., Kumamoto, 862-0976, Japan., Masunaga T; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Tateishi H; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan., Otsuka M; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan; Research and Development, Science Farm Ltd., Kumamoto, 862-0976, Japan., Yamaguchi Y; Environmental Safety Center, Kumamoto University, Kumamoto, 860-8555, Japan., Fujita M; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan; Department of Molecular Biology and Genetics, Burdur Mehmet Akif Ersoy University, Burdur, 15200, Turkey. Electronic address: mfujita@kumamoto-u.ac.jp. |
| Πηγή: | Virology [Virology] 2026 Oct; Vol. 623, pp. 111016. Date of Electronic Publication: 2026 Jun 29. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Academic Press Country of Publication: United States NLM ID: 0110674 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0341 (Electronic) Linking ISSN: 00426822 NLM ISO Abbreviation: Virology Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, Academic Press. |
| Ιατρικοί όροι (MeSH): | Viral Regulatory and Accessory Proteins*/genetics , Viral Regulatory and Accessory Proteins*/metabolism , Viral Regulatory and Accessory Proteins*/chemistry , HIV-2*/genetics , HIV-2*/physiology , HIV-2*/metabolism , vpr Gene Products, Human Immunodeficiency Virus*/genetics , vpr Gene Products, Human Immunodeficiency Virus*/metabolism , vpr Gene Products, Human Immunodeficiency Virus*/chemistry , Peptides*/metabolism , Peptides*/genetics , Peptides*/chemistry , Protein Multimerization* , Gene Expression Regulation, Viral* , Protein Biosynthesis*, Macrophages/virology ; Humans ; Amino Acid Motifs ; Cell Line ; Virus Replication |
| Περίληψη: | Human immunodeficiency virus type 2 (HIV-2) encodes the Vpx and Vpr proteins. Although these proteins are homologous, Vpx is expressed at substantially higher levels than those of Vpr. This difference can be explained by the presence of a zinc-binding site and a poly-proline motif (PPM) consisting of seven consecutive prolines, both of which are present in Vpx but absent in Vpr. This study aims to elucidate the mechanism by which the PPM regulates Vpx/Vpr expression. Experiments using point mutants at positions P108 and P109 (the last proline of the PPM) in Vpx showed that P109 is critical for replication in macrophages and is important for achieving sufficient expression levels and dimerization capacity of the Vpx protein, compared with P108. In contrast, introduction of the PPM into the Vpr protein increased its expression level in an in vitro transcription/translation system while decreasing mRNA expression. In addition, no significant increase in protein stability was detected. These results, together with additional mutational analyses, demonstrate that introduction of the PPM enhances translation of the Vpr protein. In contrast, introduction of the PPM into Human immunodeficiency virus type 1 (HIV-1) Vif did not increase expression levels. Furthermore, a synthetic peptide containing seven consecutive prolines did not bind to immunoprecipitated Vpx protein. Overall, Vpx dimerization is not considered to be caused by dimerization of the PPM region. Collectively, these findings indicate that the PPM of Vpx enhances protein dimerization, leading to increased stability, and that introduction of the PPM into Vpr enhances its translation. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: HIV-2; Poly-proline; Protein dimerization; Translation; Vpr; Vpx |
| Substance Nomenclature: | 0 (Viral Regulatory and Accessory Proteins) 0 (VPX protein, Human immunodeficiency virus 2) 0 (vpr Gene Products, Human Immunodeficiency Virus) 25191-13-3 (polyproline) 0 (Peptides) 0 (vpr protein, Human immunodeficiency virus 2) |
| Entry Date(s): | Date Created: 20260707 Date Completed: 20260723 Latest Revision: 20260723 |
| Update Code: | 20260724 |
| DOI: | 10.1016/j.virol.2026.111016 |
| PMID: | 42413395 |
| Βάση Δεδομένων: | MEDLINE |
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