Macropinosomes are a site of HIV-1 entry into primary CD4+T cells

• 成果类型: Article
• 署名作者: Murakami, Tomoyuki; Cardoso, Ricardo de Souza; Manivannan, Praveen; Chang, Ya - Ting; Rentchler, Eric; Chou, Kai - Neng; Tang, Yipei; Swanson, Joel A.; King, Philip D.; Ono, Akira
• 署名单位: University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8725
• DOI: 10.1073/pnas.2417676122
• 发表日期: 2025-06-10
• 关键词: comparing bulk endocytosis; functional readouts; disulfide bond; coated pit; t-cells; virus; fusion; macropinocytosis; infection; membrane

摘要

HIV-1 has been observed to enter target cells at both the plasma membrane and endosomes. However, which pathways mediate its entry into primary CD4+T cells, the major targets of this virus, remains unclear. Here, we show that HIV-1 can enter primary CD4+ T cells through macropinocytosis, a form of endocytosis. We found that HIV-1 can enter primary CD4+ T cells at both the plasma membrane and internal compartments, while entry into common T cell lines occurred primarily at the plasma membrane. Inhibition of macropinocytosis suppressed HIV-1 internalization into and subsequent fusion with primary CD4+ T cells regardless of the viral coreceptor usage. Microscopic analysis of viral contents exposed to the cytosol confirmed that HIV-1 fusion occurs at the macropinosomal membrane. Finally, the inhibition of macropinocytosis blocked HIV-1 infection of primary CD4+ T cells. Altogether, this study identifies macropinocytosis as one pathway for HIV-1 entry into primary CD4+ T cells.