10.1021/acsnano.7b00275.s009
Qin Li
Qin
Li
Wei Li
Wei
Li
Wen Yin
Wen
Yin
Jia Guo
Jia
Guo
Zhi-Ping Zhang
Zhi-Ping
Zhang
Dejun Zeng
Dejun
Zeng
Xiaowei Zhang
Xiaowei
Zhang
Yuntao Wu
Yuntao
Wu
Xian-En Zhang
Xian-En
Zhang
Zongqiang Cui
Zongqiang
Cui
Single-Particle
Tracking of Human Immunodeficiency Virus Type 1 Productive Entry into
Human Primary Macrophages
American Chemical Society
2017
accessory protein Vpr-conjugated QDs
drug inhibition assays
particles encapsulating QDs
Rab 5A endosomes
infection
envelope-mediated endosomal fusion
entry pathway
virus
Human Immunodeficiency Virus Type 1 Productive Entry
macrophage
HIV
2017-04-03 00:00:00
Media
https://acs.figshare.com/articles/media/Single-Particle_Tracking_of_Human_Immunodeficiency_Virus_Type_1_Productive_Entry_into_Human_Primary_Macrophages/4823398
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.