Cited by 100HIV Research and TreatmentCellular transport and secretionHIV/AIDS Research and Interventions

Human Immunodeficiency Virus type 1 Endocytic Trafficking Through Macrophage Bridging Conduits Facilitates Spread of Infection

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Kadiu, Irena, Gendelman, Howard E.·2011·Journal of Neuroimmune Pharmacology

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.

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Authors
Kadiu, I., & Gendelman, H. E.
Affiliations
Nebraska Medical Center (US)
Corresponding author
Gendelman, Howard E.
Venue
Journal of Neuroimmune Pharmacology
Published
2011-07-26
Volume
6
Issue
4
Pages
658-675
ISSN
  • 1557-1890 (ISSN-L)
  • 1557-1904
OpenAlex
W2062874567
Cited by
100
References
58
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 9 · 2013: 6 · 2012: 8
FWCI
2.91
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Journal of Neuroimmune Pharmacology (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (RR15635, DA028555)
  • National Institute of Mental Health (P01 MH 64570, P30MH062261, P01MH064570)
  • National Institute on Drug Abuse (P01DA028555, P20DA026146, P01DA026146)
  • National Institute of Neurological Disorders and Stroke (R01-NS-36126, P01-NS31492, P01 NS 43985, R01NS036126, P01NS031492, P01NS043985, R01NS034239)
  • National Center for Research Resources (P20 RR-15635, P20RR015635)
  • National Institute on Minority Health and Health Disparities (G12MD007600)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
Keywords
HIV-1, macrophages, cell-to-cell viral spread, endosomal trafficking, multivesicular bodies, myosin II, cytoskeleton
MeSH terms
Cell Communication, Endocytosis, Humans, Immunohistochemistry, Macrophages, Microscopy, Electron, Endosomes, HIV-1, HIV Infections, In Situ Hybridization, Fluorescence, Microscopy, Confocal

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