Functional Role of O-Glycosylation of HIV-1

HIV-1 O-糖基化的功能作用

• 批准号: 8534995
• 负责人: Ronald C Desrosiers
• 金额: $ 5.26万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-15 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8534995
• 关键词: Acquired Immunodeficiency Syndrome; Amino Acids; Antiviral Agents; Binding; Biochemical; Biological Assay; C-terminal; Carbohydrates; Complex; Development; Evolution; Family; HIV Envelope Protein gp120; HIV-1; Influenza; Influenza A Virus, H5N1 Subtype; Influenza A virus; Laboratories; Link; Location; Membrane Glycoproteins; Molecular; Pathogenesis; Peptides; Positioning Attribute; Post-Translational Protein Processing; Proteins; Role; SIV; Serine; Site-Directed Mutagenesis; Structure; Surface; Threonine; Viral; Virion; Virus; drug development; glycosylation; high throughput screening; influenzavirus; inhibitor/antagonist; interest; receptor binding; research study; screening; small molecule; vaccine development

Highly conserved threonine residues were noted near the C-terminus of the external surface glycoproteins of HIV-1, SIV, and influenza A virus; this threonine residue was shown to be the efficient target of O-glycosylation on all three viruses. In all three cases, this O-glycosylated threonine was essential for the infectivity of the virus. We will define the functional role of C-terminal threonine glycosylation for HIV-1 and we will develop assays amenable to high throughput screening for the development of antiviral drugs. We will delineate protein-peptide and peptide-peptide interactions that are dependent on the O-glycosylated threonine of gp120. We will also examine whether there are rare examples of naturally-occurring HIV-1 sequences that are functional without an O-glycosylated threonine at this location.

在 HIV-1、SIV 和甲型流感病毒的外表面糖蛋白 C 末端附近发现了高度保守的苏氨酸残基；该苏氨酸残基被证明是所有三种病毒上 O-糖基化的有效靶点。在所有这三种情况下，这种 O-糖基化苏氨酸对于病毒的感染性至关重要。我们将确定 HIV-1 C 末端苏氨酸糖基化的功能作用，并开发 适用于抗病毒药物开发的高通量筛选的测定。我们将描述依赖于 gp120 的 O-糖基化苏氨酸的蛋白质-肽和肽-肽相互作用。我们还将检查是否存在天然存在的 HIV-1 序列的罕见例子，该序列在该位置没有 O-糖基化苏氨酸的情况下仍具有功能。