SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells

Abstract The dynamic interplay between dendritic cells (DCs) and human immunodeficiency virus type-1 (HIV-1) is thought to result in viral dissemination and evasion of antiviral immunity. Although initial observations suggested that the C-type lectin receptor (CLR) DC-SIGN was responsible for the trans-infection function of the virus, subsequent studies demonstrated that trans-infection of CD4+ T cells with HIV-1 can also occur through DC-SIGN–independent mechanisms. We demonstrate that a cell surface molecule designated DCIR (for DCimmunoreceptor), a member of a recently described family of DC-expressing CLRs, can participate in the capture of HIV-1 and promote infection in trans and in cis of autologous CD4+ T cells from human immature monocyte-derived DCs. The contribution of DCIR to these processes was revealed using DCIR-specific siRNAs and a polyclonal antibody specific for the carbohydrate recognition domain of DCIR. Data from transfection experiments indicated that DCIR acts as a ligand for HIV-1 and is involved in events leading to productive virus infection. Finally, we show that the neck domain of DCIR is important for the DCIR-mediated effect on virus binding and infection. These results point to a possible role for DCIR in HIV-1 pathogenesis by supporting the productive infection of DCs and promoting virus propagation.

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Kaposi's-sarcoma-associated-herpesvirus-activated dendritic cells promote HIV-1 trans-infection and suppress CD4+ T cell proliferation

Virology ◽

10.1016/j.virol.2013.02.018 ◽

2013 ◽

Vol 440 (2) ◽

pp. 150-159 ◽

Cited By ~ 1

Author(s):

Wan Liu ◽

Yan Qin ◽

Lei Bai ◽

Ke Lan ◽

Jian-Hua Wang

Keyword(s):

Cell Proliferation ◽

Dendritic Cells ◽

T Cell ◽

Kaposi's Sarcoma ◽

Kaposi’S Sarcoma ◽

Cd4 T Cell ◽

T Cell Proliferation ◽

Trans Infection ◽

Kaposi’S Sarcoma Associated Herpesvirus ◽

Hiv 1

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922 HIV-1 trans-infection of T-cells via dendritic cells requires endosomal sorting and polarized trafficking to the virological synapse

Journal of Investigative Dermatology ◽

10.1016/j.jid.2018.03.934 ◽

2018 ◽

Vol 138 (5) ◽

pp. S157

Author(s):

R. Bayliss ◽

J. Wheeldon ◽

S. Caucheteux ◽

C. Niessen ◽

V. Piguet

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Virological Synapse ◽

Endosomal Sorting ◽

Trans Infection ◽

Polarized Trafficking ◽

Hiv 1

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Uterine Epithelial Cell Regulation of DC-SIGN Expression Inhibits Transmitted/Founder HIV-1 Trans Infection by Immature Dendritic Cells

PLoS ONE ◽

10.1371/journal.pone.0014306 ◽

2010 ◽

Vol 5 (12) ◽

pp. e14306 ◽

Cited By ~ 25

Author(s):

Daniel O. Ochiel ◽

Christina Ochsenbauer ◽

John C. Kappes ◽

Mimi Ghosh ◽

John V. Fahey ◽

...

Keyword(s):

Dendritic Cells ◽

Epithelial Cell ◽

Cell Regulation ◽

Uterine Epithelial Cell ◽

Immature Dendritic Cells ◽

Trans Infection ◽

Hiv 1

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Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway

Blood ◽

10.1182/blood-2008-05-158642 ◽

2009 ◽

Vol 113 (12) ◽

pp. 2732-2741 ◽

Cited By ~ 148

Author(s):

Nuria Izquierdo-Useros ◽

Mar Naranjo-Gómez ◽

Jacob Archer ◽

Steven C. Hatch ◽

Itziar Erkizia ◽

...

Keyword(s):

Dendritic Cells ◽

T Lymphocytes ◽

T Cell Activation ◽

Cell Activation ◽

Fluorescent Protein ◽

Independent Manner ◽

Trans Infection ◽

Immunodeficiency Virus ◽

Green Fluorescent ◽

Hiv 1

AbstractExosomes are secreted cellular vesicles that can be internalized by dendritic cells (DCs), contributing to antigen-specific naive CD4+ T-cell activation. Here, we demonstrate that human immunodeficiency virus type 1 (HIV-1) can exploit this exosome antigen-dissemination pathway intrinsic to mature DCs (mDCs) for mediating trans-infection of T lymphocytes. Capture of HIV-1, HIV-1 Gag-enhanced green fluorescent protein (eGFP) viral-like particles (VLPs), and exosomes by DCs was up-regulated upon maturation, resulting in localization within a CD81+ compartment. Uptake of VLPs or exosomes could be inhibited by a challenge with either particle, suggesting that the expression of common determinant(s) on VLP or exosome surface is necessary for internalization by mDCs. Capture by mDCs was insensitive to proteolysis but blocked when virus, VLPs, or exosomes were produced from cells treated with sphingolipid biosynthesis inhibitors that modulate the lipid composition of the budding particles. Finally, VLPs and exosomes captured by mDCs were transmitted to T lymphocytes in an envelope glycoprotein-independent manner, underscoring a new potential viral dissemination pathway.

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Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Infection by Activating Primary CD4+ T Cells

PLoS ONE ◽

10.1371/journal.pone.0027609 ◽

2011 ◽

Vol 6 (11) ◽

pp. e27609 ◽

Cited By ~ 10

Author(s):

Yan Qin ◽

Yuye Li ◽

Wan Liu ◽

Renrong Tian ◽

Qianqian Guo ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Viral Infection ◽

Cd4 T Cells ◽

Penicillium Marneffei ◽

Trans Infection ◽

Hiv 1

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Dendritic Cells and HIV-1 Trans-Infection

Viruses ◽

10.3390/v2081704 ◽

2010 ◽

Vol 2 (8) ◽

pp. 1704-1717 ◽

Cited By ~ 36

Author(s):

David McDonald

Keyword(s):

Dendritic Cells ◽

Trans Infection ◽

Hiv 1

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Slit2N Inhibits Transmission Of HIV-1 From Dendritic Cells To T-Cells By Modulating Novel Cytoskeletal Elements

Blood ◽

10.1182/blood.v122.21.2285.2285 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2285-2285

Author(s):

Ashutosh Shrivastava ◽

Anil Prasad ◽

Paula Kuzontkoski ◽

Jinlong Yu ◽

Jerome E. Groopman

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Conflicts Of Interest ◽

Target Cells ◽

Dependent Manner ◽

Trans Infection ◽

Intact Virus ◽

Cell Transmission ◽

Cytoskeletal Elements ◽

Hiv 1

Abstract During sexual contact, HIV-1 can enter the mucous membranes of the vagina, throat, or rectum. There, the virus encounters potential target cells, including antigen-presenting cells such as dermal dendritic cells (DC), Langerhans cells, and plasmacytoid DCs, which play pivotal roles in both innate and adaptive immunity. All DC subsets are susceptible to HIV-1 infection or internalization of intact virus, and appear to facilitate cell-mediated transmission of HIV-1 in the mucosa and lymphatic tissues. Once internalized, HIV-1 can be transmitted from DCs to T-cells at a specialized junction termed the infectious synapse (IS). Recent studies reveal that several actin-rich DC membrane extensions, including actin filopodia, membrane sheets, cytonemes, and nanotubes, establish direct contact between cells at the IS and facilitate HIV-1 transmission. Although the virus can infect T-cells directly (cis-infection), transmission of HIV-1 from DCs to T-cells at IS (trans-infection and de novo trans-infection) appears to be some 10 to 100 times more efficient than direct infection; therefore, cell-to-cell transmission is an attractive target for novel HIV therapeutics. We evaluated the effects of Slit2N, a ligand for the Roundabout (Robo) receptors, on the transmission of HIV-1 from DCs to T-cells. Slit2N inhibits HIV-1 transmission to T-cells and its replication. Binding of HIV-1 to DC-SIGN on the surface of DCs initiates signaling through cellular-Src (c-Src) and cell division control protein 42 (Cdc42), which modulates actin polymerization and filopodia formation via the actin-related protein 2/3 (Arp2/3) complex and mammalian Diaphanous 2 (mDia2). Slit2N inhibited HIV-1-induced signaling through both Arp2/3 and mDia2, decreased filopodial extensions on virus-infected DCs, and inhibited cell-to-cell transmission of HIV-1 at the IS in a Robo1-dependent manner. Of particular note, we identified Flightless-1 (Fli1) as a novel, Robo1-interacting protein, and demonstrated that it is required for efficient cell-to-cell transmission of HIV-1. These results suggest that targeting the Slit/Robo pathway involves the modulation of previously unrecognized cytoskeletal elements in HIV-1 transmission, and thus, offers an innovative strategy to limit viral infection in the host. Disclosures: No relevant conflicts of interest to declare.

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