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[Study of molecular function of proteins in human immunodeficiency virus].

Abstract
Human immunodeficiency virus (HIV) has no more than nine genes expressing approximately twenty proteins. When T lymphocytes and macrophages in a body are infected with HIV, these proteins work in turn at specific time and location, causing acquired immunodeficiency syndrome (AIDS), a disease yet to be overcome. Since the elucidation of molecular mechanism of HIV proteins should lead to remedy of AIDS, the author has been engaged in the study of HIV protein in the past decade. Described herein are viral protein X (Vpx), uniquely found in HIV-2, and its homologous protein Vpr found both in HIV-1 and -2. We found that Vpx enhances genome nuclear import in T lymphocytes, and is critical for reverse transcription of viral RNA in macrophages. This finding on the function in macrophages corrected long-term misleading belief. Furthermore, functional region mapping of Vpx was performed. In 2011, the protein SAMHD1 was identified as the host restriction factor counteracted by Vpx, by foreign researchers. After that, our independent study demonstrated the presence of SAMHD1-independent functions of Vpx in T cells, in addition to its SAMHD1-dependent functions in macrophages. Another topic of this review is Gag protein. Recently, it has reported by overseas researchers that PI(4,5)P2 (one of phosphoinositide) regulates Pr55(Gag) localization and assembly. In this study, we determined the binding affinity between N-terminal MA domain of Pr55(Gag) and various phosphoinositide derivatives using surface plasmon resonance. The results suggested that both negatively charged inositol phosphates and hydrophobic acyl chain are required for the MA binding.
AuthorsMikako Fujita
JournalYakugaku zasshi : Journal of the Pharmaceutical Society of Japan (Yakugaku Zasshi) Vol. 133 Issue 10 Pg. 1103-11 ( 2013) ISSN: 1347-5231 [Electronic] Japan
PMID24088354 (Publication Type: Journal Article, Review)
Chemical References
  • Phosphatidylinositols
  • Protein Precursors
  • RNA, Viral
  • VPX protein, Human immunodeficiency virus 2
  • Viral Regulatory and Accessory Proteins
  • p55 gag precursor protein, Human immunodeficiency virus 1
  • vpr Gene Products, Human Immunodeficiency Virus
  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human
  • Monomeric GTP-Binding Proteins
Topics
  • Acquired Immunodeficiency Syndrome (virology)
  • Active Transport, Cell Nucleus
  • Drug Discovery
  • Genome, Viral
  • HIV-1 (genetics)
  • HIV-2 (genetics)
  • Macrophages (virology)
  • Molecular Targeted Therapy
  • Monomeric GTP-Binding Proteins (physiology)
  • Phosphatidylinositols (chemistry, metabolism, physiology)
  • Protein Binding
  • Protein Precursors (metabolism)
  • Protein Structure, Tertiary
  • Protein Transport
  • RNA, Viral (genetics)
  • Reverse Transcription
  • SAM Domain and HD Domain-Containing Protein 1
  • Surface Plasmon Resonance
  • T-Lymphocytes (virology)
  • Viral Regulatory and Accessory Proteins (genetics, physiology)
  • vpr Gene Products, Human Immunodeficiency Virus (genetics, physiology)

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