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| Content Provider | Springer Nature Link |
|---|---|
| Author | Kadiu, Irena Gendelman, Howard E. |
| Copyright Year | 2011 |
| Abstract | Bridging conduits (BC) sustain communication and homeostasis between distant tethered cells. These are also exploited commonly for direct cell-to-cell transfer of microbial agents. Conduits efficiently spread infection, effectively, at speeds faster than fluid phase exchange while shielding the microbe against otherwise effective humoral immunity. Our laboratory has sought to uncover the mechanism(s) for these events for human immunodeficiency virus type one (HIV-1) infection. Indeed, in our prior works HIV-1 Env and Gag antigen and fluorescent virus tracking were shown sequestered into endoplasmic reticulum-Golgi organelles but the outcomes for spreading viral infection remained poorly defined. Herein, we show that HIV-1 specifically traffics through endocytic compartments contained within BC and directing such macrophage-to-macrophage viral transfers. Following clathrin-dependent viral entry, HIV-1 constituents bypass degradation by differential sorting from early to Rab11$^{+}$ recycling endosomes and multivesicular bodies. Virus-containing endocytic viral cargoes propelled by myosin II through BC spread to neighboring uninfected cells. Disruption of endosomal motility with cytochalasin D, nocodasole and blebbistatin diminish intercellular viral spread. These data lead us to propose that HIV-1 hijacks macrophage endocytic and cytoskeletal machineries for high-speed cell-to-cell spread. |
| Starting Page | 658 |
| Ending Page | 675 |
| Page Count | 18 |
| File Format | |
| ISSN | 15571890 |
| Journal | Journal of Neuroimmune Pharmacology |
| Volume Number | 6 |
| Issue Number | 4 |
| e-ISSN | 15571904 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2011-07-26 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | HIV-1 Macrophage Bridging conduits Tunneling nanotubes Recycling endosomes Multivesicular bodies Viral trafficking Endocytic sorting Lysosomes Early endosomes Motor proteins Tubulin Intercellular viral spread Virology Neurosciences Immunology Cell Biology Pharmacology/Toxicology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Allergy Pharmacology Immunology |
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