SARS-CoV-2 and HIV-1 Interactions with C-Type Lectins

SARS-CoV-2 和 HIV-1 与 C 型凝集素的相互作用

• 批准号: 10486854
• 负责人: vineet n kewalramani
• 金额: $ 35.7万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10486854
• 关键词: 2019-nCoV; ACE2; Affect; Alleles; Binding; C Type Lectin Receptors; C-Type Lectins; CD209 gene; Cells; Coculture Techniques; Endothelial Cells; HIV-1; Infection; Lentivirus Vector; Lung; Pathway interactions; Predisposition; Proteins; Receptor Activation; SARS-CoV-2 infection; SARS-CoV-2 spike protein; SARS-CoV-2 variant; Serine Protease; System; TMPRSS2 gene; Tissues; alveolar type II cell; cell transformation; neutralizing antibody; receptor; respiratory; virus envelope

Using lentiviral vectors pseudotyped with SARS-CoV-2 Spike protein, we are examining different SARS-CoV-2 variants for their ability to interact with CLEC4M, and whether this interaction facilitates direct infection of cells or efficient transfer and infection of cells expressing canonical SARS-CoV-2 entry and activation receptors. Different allelic forms of CLEC4M appear to support the direct infection of cells expressing the C-type lectin by the pseudoviruses in a manner that is dependent on Spike interaction with CLEC4M. We are (1) studying the domains of CLEC4M that bind the Spike protein, (2) the efficiency of transfer to target cells, (3) susceptibility to neutralizing antibodies, and (4) whether CLEC4M affects the neutralization of Spike variants of SARS-CoV-2 is effected in a coculture system.

使用慢病毒载体对SARS-COV-2尖峰蛋白进行伪型，我们正在检查不同的SARS-COV-2变体与Clec4M相互作用的能力，以及这种相互作用是否促进了细胞的直接感染，有效地转移和感染细胞的细胞表达Canonical SARS-COV-2进入和活性受体。不同的等位基因形式的CLEC4M似乎支持通过伪病毒表达C型凝集素的细胞的直接感染，其方式取决于与CLEC4M相互作用的峰值相互作用。 （1）研究结合尖峰蛋白的CLEC4M域，（2）转移到靶细胞的效率，（3）对中和抗体的敏感性，以及（4）Clec4M是否影响SARS-COV-2的中和SARS-COV-2的中和化。