HIV-1 targets L-selectin for adhesion and induces its shedding for viral release

Kononchik, Joseph; Ireland, Joanna; Zou, Zhongju; Segura, Jason; Holzapfel, Genevieve; Chastain, Ashley M.; Wang, Ruipeng; Spencer, Matthew; He, Biao; Stutzman, Nicole; Kano, Daiji; Arthos, James; Fischer, Elizabeth R.; Chun, Tae‐Wook; Moir, Susan; Sun, Peter D.

doi:10.1038/s41467-018-05197-2

Cited by 17 publications

(48 citation statements)

References 68 publications

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“…We have shown that L-, Pand E-selectins bind to purified EBOV-GP coated on ELISA plates and to EBOV-GP transfected cells (HEK-293 and CHO-K1). This is confirmed by recently published data that the viral particle gp120 of HIV-1 binds L-selectin (CD62L) (84)(85)(86)(87). Similarly, human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71 (180).…”

Section: Ebov-gp Protects Hek-293 Cells From Lysis By Polyclonal Nk Csupporting

confidence: 78%

“…We conclude that selectins play an important role in virus release from infected cells, as it has been shown for HIV, which binds L-selectin and CD34 to co-localize with ADAM17 (84)(85)(86)(87). Glycans designated sialyl 6-sulfo Lewis x carbohydrate are potential ligands for selectins [15].…”

Section: Ebov-gp Protects Hek-293 Cells From Lysis By Polyclonal Nk Cmentioning

confidence: 59%

“…The glycoprotein gp120 of HIV-1 binds L-selectin in solution and on the host cell membrane. Upon entry of HIV into CD4 + T cells, L-selectin is cleaved at the membrane proximal site by proteolysis, thus facilitating virus release from cells (84,85). L-selectin is clustered with Eselectin and CD34 in trans (86,87), whereby co-localization of L-selectin with ADAM17 is induced to the uropod (85).…”

Section: Introductionmentioning

confidence: 99%

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Activating NK- receptors, homing selectins and inhibitory Siglecs recognize EBOLA-GP and HPV-L1NK

Jarahian

Marstaller

Wurmbäck

et al. 2020

Preprint

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The Ebola virus glycoprotein (EBOV)-GP is extensively glycosylated. Its expression induces a physical alteration of surface adhesion molecules, which causes cell rounding and detachment of the infected cells. This phenomenon likely plays a crucial role in viral pathogenicity. In this study, we show that such morphological changes are cell line-dependent as well as dependent on the surface proteins that interact with EBOV-GP in cis and trans. We have generated data showing that natural killer (NK) cell receptors (NCRs: NKp44 and NKp46), selectins (CD62E/P/L) and inhibitory Siglecs function as receptors for Ebola-GP and human papilloma virus (HPV-L1). We used HEK293 cells transfected with Ebola-GP and recombinant fusion proteins containing the extracellular domain of each of these receptors linked to the Fc of human IgG1, which showed significant differences in their virus-binding behavior compared to HEK293 cells transfected with empty vector. Further, to demonstrate that EBOV-GP is a ligand for NKp44 and other NK-receptors, and to investigate their role in immune escape, we also used human HEK-293, HeLa- and hamster CHO-GP-transfectants. Our data show that the NK receptors NKp44 and NKp46 play a key role in recognizing EBOV (Ebolavirus) and strongly suggest that other inhibitory (Siglec-7, Siglec-5) and non-inhibitory homing receptors (P-Selectin, L-Selectin, E-Selectin, and DC-SIGNR/DC-SIGN) take part in the interaction with virus particles. In addition, we show that NKp44, and NKp46, Siglec-7, and -5, and P-, L-, E-selectins as well as of and DC-SIGNR/DC-SIGN bind to the artificial viral envelope of a lentiviral vector that contains EBOV-GP. Altogether we prove that NCRs and a range of other inhibitory and activating receptors can interact with viral envelope/capsid proteins and that such interaction could play an important role in the elimination of virus infected cells. Our findings could be used to develop new strategies for prevention and treatment of infections by these viruses.Author summaryThe innate immune system is able to recognize specifically certain virus components. Here we show that activating NK-cell receptors (NKp44, and NKp46) are involved in such interaction by using HEK293 and CHOK1 cells transfected with the Ebola virus glycoprotein (EBOV-GP) and by binding studies with purified EBOV-GP. In detail, we have found moderate to strong affinity of Siglecs (Siglec-7, and -5), selectins (P-, L-, E-Selectin) and DC-SIGNR/DC-SIGN to purified EBOV-GP, and to cells transfected with EBOV-GP as well as to the envelope of a lentiviral vector carrying the EBOV-GP. Our findings show that NKp44, and NKp46, Siglec-7, and -5, as well as P-and L-selectins have a strong affinity to EBOV-G.

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Section: Ebov-gp Protects Hek-293 Cells From Lysis By Polyclonal Nk Csupporting

confidence: 78%

Section: Ebov-gp Protects Hek-293 Cells From Lysis By Polyclonal Nk Cmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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Activating NK- receptors, homing selectins and inhibitory Siglecs recognize EBOLA-GP and HPV-L1NK

Jarahian

Marstaller

Wurmbäck

et al. 2020

Preprint

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“…Such post-translational mechanisms of reducing L-selectin surface expression by HIV is thought to prevent trafficking back to secondary lymphoid organs, redirecting infected T-cells to the systemic circulation to increase viremia. L-selectin expression on naive CD4 T-cells has recently been defined as a novel receptor for HIV entry (58), and work from this study reveals that L-selectin shedding ensues 4–6 days post-infection. Moreover, HIV preferentially infects T CM over T EM cells – positively correlating with L-selectin expression.…”

Section: Regulation Of L-selectin Protein Expression In Divergent Leumentioning

confidence: 77%

L-selectin: A Major Regulator of Leukocyte Adhesion, Migration and Signaling

2019

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L-selectin (CD62L) is a type-I transmembrane glycoprotein and cell adhesion molecule that is expressed on most circulating leukocytes. Since its identification in 1983, L-selectin has been extensively characterized as a tethering/rolling receptor. There is now mounting evidence in the literature to suggest that L-selectin plays a role in regulating monocyte protrusion during transendothelial migration (TEM). The N-terminal calcium-dependent (C-type) lectin domain of L-selectin interacts with numerous glycans, including sialyl Lewis X (sLe x ) for tethering/rolling and proteoglycans for TEM. Although the signals downstream of L-selectin-dependent adhesion are poorly understood, they will invariably involve the short 17 amino acid cytoplasmic tail. In this review we will detail the expression of L-selectin in different immune cell subsets, and its influence on cell behavior. We will list some of the diverse glycans known to support L-selectin-dependent adhesion, within luminal and abluminal regions of the vessel wall. We will describe how each domain within L-selectin contributes to adhesion, migration and signal transduction. A significant focus on the L-selectin cytoplasmic tail and its proposed contribution to signaling via the ezrin-radixin-moesin (ERM) family of proteins will be outlined. Finally, we will discuss how ectodomain shedding of L-selectin during monocyte TEM is essential for the establishment of front-back cell polarity, bestowing emigrated cells the capacity to chemotax toward sites of damage.

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“…In addition, some Siglecs—Siglec‐3 both on HL‐60 and on granulocyte, Siglec‐5 and Siglec‐9 on granulocyte—were found. L‐Selectin, which is involved in migration of leukocytes, generally recognizes sialyl Lewis oligosaccharide structures on glycoproteins and/or glycolipids and interacts weakly with sialyl lactose . On the other hand, Siglecs, which are involved in cell–cell interaction and immune response, recognize sialyl oligosaccharide structures containing SAα2‐3Gal and SAα2‐6Gal motifs .…”

Section: Resultsmentioning

confidence: 99%

Cell Profiling Based on Sugar‐Chain–Cell Binding Interaction and Its Application to Typing and Quality Verification of Cells

et al. 2019

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Developing methods to determine cell type and cell state has been a significant challenge in the field of cancer diagnosis as well as in typing and quality verification for cultured cells. Herein, we report a cell profiling method based on binding interactions between cell‐surface sugar‐chain‐binding proteins and sugar‐chain‐immobilized fluorescent nanoparticles (SFNPs), together with a method for cell typing and cell quality verification. Binding profiles of cells against sugar chains were analyzed by performing flow cytometry analysis with SFNPs. Discrimination analysis based on binding profiles could classify cell type and evaluate the quality of cultured cells. By applying our method to differentiated cells originating from conventional cell lines and also to mouse embryotic stem cells, we could detect the cells before and after differentiation. Our method can be utilized not only for the biofunctional analysis of cells but also for diagnosis of cancer cells and quality verification of cultured cells.

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HIV-1 targets L-selectin for adhesion and induces its shedding for viral release

Cited by 17 publications

References 68 publications

Activating NK- receptors, homing selectins and inhibitory Siglecs recognize EBOLA-GP and HPV-L1NK

Activating NK- receptors, homing selectins and inhibitory Siglecs recognize EBOLA-GP and HPV-L1NK

L-selectin: A Major Regulator of Leukocyte Adhesion, Migration and Signaling

Cell Profiling Based on Sugar‐Chain–Cell Binding Interaction and Its Application to Typing and Quality Verification of Cells

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