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Cited by 115HIV Research and TreatmentCellular Mechanics and InteractionsT-cell and Retrovirus Studies

Mobilization of HIV Spread by Diaphanous 2 Dependent Filopodia in Infected Dendritic Cells

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Aggarwal, Anupriya, Iemma, Tina L., Shih, Ivy, Newsome, Timothy P., McAllery, Samantha, Cunningham, Anthony L., Turville, Stuart G.·2012·PLoS Pathogens
DOI 10.1371/journal.ppat.1002762PMC PMC3369929
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Abstract

Paramount to the success of persistent viral infection is the ability of viruses to navigate hostile environments en route to future targets. In response to such obstacles, many viruses have developed the ability of establishing actin rich-membrane bridges to aid in future infections. Herein through dynamic imaging of HIV infected dendritic cells, we have observed how viral high-jacking of the actin/membrane network facilitates one of the most efficient forms of HIV spread. Within infected DC, viral egress is coupled to viral filopodia formation, with more than 90% of filopodia bearing immature HIV on their tips at extensions of 10 to 20 µm. Live imaging showed HIV filopodia routinely pivoting at their base, and projecting HIV virions at µm.sec⁻¹ along repetitive arc trajectories. HIV filopodial dynamics lead to up to 800 DC to CD4 T cell contacts per hour, with selection of T cells culminating in multiple filopodia tethering and converging to envelope the CD4 T-cell membrane with budding HIV particles. Long viral filopodial formation was dependent on the formin diaphanous 2 (Diaph2), and not a dominant Arp2/3 filopodial pathway often associated with pathogenic actin polymerization. Manipulation of HIV Nef reduced HIV transfer 25-fold by reducing viral filopodia frequency, supporting the potency of DC HIV transfer was dependent on viral filopodia abundance. Thus our observations show HIV corrupts DC to CD4 T cell interactions by physically embedding at the leading edge contacts of long DC filopodial networks.

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  • Nef mediates an increase in the number of DC filopodia with immature HIV particles on their tips; filopodia scan space, cells converge, and DC wraps T cell to establish a folded VS.

    “Aggarwal et al. found that the accessory protein, Nef, mediates an increase in the number of DC filopodia with immature HIV particles on their tips [106]. Filopodia scan the space to establish contact with the T cell; then, the cells converge, and the DC wraps the T cell to establish a folded VS.”

    From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [106]

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Authors
Aggarwal, A., Iemma, T. L., Shih, I., Newsome, T. P., McAllery, S., Cunningham, A. L., & Turville, S. G.
Affiliations
  • The University of Sydney (AU)
  • UNSW Sydney (AU)
Corresponding author
Turville, Stuart G.
ORCID
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2012-06-07
Volume
8
Issue
6
Pages
e1002762
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1002762
PMC
PMC3369929
OpenAlex
W2089676893
Cited by
115
References
3
Citations by year
2026: 3 · 2025: 7 · 2024: 4 · 2023: 11 · 2022: 11 · 2021: 8 · 2020: 10 · 2019: 8 · 2018: 10 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 15 · 2013: 6 · 2012: 8
FWCI
4.73
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Medical Research Council
  • National Health and Medical Research Council (632932, 570917)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords
HIV, dendritic cells, actin cytoskeleton, HIV transmission, viral egress, NEF, CD4+ T cell infection, live imaging
MeSH terms
Formins, Carrier Proteins, Cell Line, Dendritic Cells, HIV, Host-Parasite Interactions, Humans, Pseudopodia, Virion, CD4-Positive T-Lymphocytes, Microscopy, Electron, Transmission

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