Single-Particle Tracking of Human Immunodeficiency Virus Type 1 Productive Entry into Human Primary Macrophages.

Abstract

Macrophages are one of the major targets of human immunodeficiency virus (HIV-1), but the viral entry pathway remains poorly understood in these cells. Noninvasive virus labeling and single-virus tracking are effective tools for studying virus entry. Here, we constructed a quantum dot (QD)-encapsulated infectious HIV-1 particle to track viral entry at a single-particle level in live human primary macrophages. QDs were encapsulated in HIV-1 virions by incorporating viral accessory protein Vpr-conjugated QDs during virus assembly. With the HIV-1 particles encapsulating QDs, we monitored the early phase of viral infection in real time and observed that, during infection, HIV-1 was endocytosed in a clathrin-mediated manner; the particles were translocated into Rab5A-positive endosomes, and the core was released into the cytoplasm by viral envelope-mediated endosomal fusion. Drug inhibition assays verified that endosome fusion contributes to HIV-1 productive infection in primary macrophages. Additionally, we observed that a dynamic actin cytoskeleton is critical for HIV-1 entry and intracellular migration in primary macrophages. HIV-1 dynamics and infection could be blocked by multiple different actin inhibitors. Our study revealed a productive entry pathway in macrophages that requires both endosomal function and actin dynamics, which may assist in the development of inhibitors to block the HIV entry in macrophages.

• Authors: Qin Li, Wei Li, Wen Yin, Jia Guo, Zhi-Ping Zhang, Dejun Zeng, Xiaowei Zhang, Yuntao Wu, Xian-En Zhang, Zongqiang Cui
• Journal: ACS nano (ACS Nano) Vol. 11 Issue 4 Pg. 3890-3903 (04 25 2017) ISSN: 1936-086X [Electronic] United States
• PMID: 28371581 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Cells, Cultured
• HEK293 Cells
• HIV-1 (chemistry, metabolism)
• Humans
• Macrophages (metabolism, virology)
• Optical Imaging
• Quantum Dots (chemistry, metabolism)
• Single Molecule Imaging (methods)