Functional Role of O-Glycosylation of HIV-1

HIV-1 O-糖基化的功能作用

• 批准号: 8705821
• 负责人: Ronald C Desrosiers
• 金额: $ 31.46万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 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 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705821
• 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.

高度保守的苏氨酸残基附近的C-末端的HIV-1，SIV，和甲型流感病毒的外表面糖蛋白，这苏氨酸残基被证明是有效的目标O-糖基化的所有三种病毒。在所有三种情况下，这种O-糖基化苏氨酸是病毒感染性所必需的。我们将确定C-末端苏氨酸糖基化对HIV-1的功能作用， 用于开发抗病毒药物的适合高通量筛选的测定。我们将描绘蛋白质-肽和肽-肽的相互作用，依赖于O-糖基化的苏氨酸的gp 120。我们还将研究是否有罕见的自然发生的HIV-1序列的功能没有O-糖基化苏氨酸在这个位置的例子。