scholarly journals Siglec-1 Expressed on Dendritic Cells is a New Receptor Implicated in Arenavirus Uptake

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 90
Author(s):  
Xabier Muniz-Trabudua ◽  
Cristina Borio ◽  
Marcos Bilen ◽  
Itziar Erkizia ◽  
Daniel Perez-Zsolt ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Confocal Microscopy ◽  
Antiviral Treatment ◽  
Raji Cell ◽  
T Test ◽  
Viral Envelope ◽  
Interferon Α ◽  
Enveloped Viruses ◽  
Isotype Control ◽  
Hiv 1

Arenaviruses are enveloped viruses that cause hemorrhagic fever outbreaks in humans and still lack an effective antiviral treatment. Upon early infection, these viruses target dendritic cells (DCs), which can promote systemic viral dissemination, contributing to pathogenesis. We have previously described that Siglec-1, a sialic acid Ig-like binding lectin-1 expressed on DCs interacts with different enveloped viruses and promotes their capture within a virus-containing compartment. Such is the case of HIV-1 or Ebola virus, which display sialylated gangliosides on their viral envelope that are effectively recognized by Siglec-1. Here, we aimed to study if Siglec-1 on DCs also interacts with arenaviruses such as Junin. We produced non-infectious Junin viral-like particles (Junin-VLPs) tagged with fluorescent Egfp by transfecting a plasmid encoding the structural Junin Z protein on HEK-293T cells. Junin-VLPs were added to a Raji cell line stably transfected with Siglec-1 or to monocyte-derived DCs activated or not with either Interferon-α or lipopolysaccharide. Viral uptake was analyzed by FACS or confocal microscopy in the presence of an anti-Siglec-1 monoclonal antibody (mAb) or an isotype control. Statistical differences were assessed with the indicated tests. Raji Siglec-1 cells captured a higher number of Junin-VLPs than Raji cells, and this was blocked with an anti-Siglec-1 mAb (P = 0.0159; Mann–Whitney). On primary DCs, activation enhanced Junin-VLP capture (P = 0.0024; paired t-test) and Siglec-1 expression. Furthermore, pre-incubation with an anti-Siglec-1 mAb on activated DCs blocked Junin-VLP uptake (P ≤ 0.0002; one sample t-test), while an isotype control did not. Forty-nine percent of the activated DCs analyzed by confocal microscopy captured Junin-VLPs within a Siglec-1+ virus-containing compartment. Moreover, when HIV-1 was also added, 97% of those compartments retained both viruses. Thus, we conclude that Siglec-1 is a new receptor involved in arenavirus uptake in DCs and could represent a novel target for an anti-arenavirus treatment.

scholarly journals Differential Transmission of Human Immunodeficiency Virus Type 1 by Distinct Subsets of Effector Dendritic Cells

2002 ◽  
Vol 76 (15) ◽  
pp. 7812-7821 ◽  
Author(s):  
Rogier W. Sanders ◽  
Esther C. de Jong ◽  
Christopher E. Baldwin ◽  
Joost H. N. Schuitemaker ◽  
Martien L. Kapsenberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Dendritic Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Virus Transmission ◽  
Viral Envelope ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Dendritic cells (DC) support human immunodeficiency virus type 1 (HIV-1) transmission by capture of the virus particle in the mucosa and subsequent transport to the draining lymph node, where HIV-1 is presented to CD4+ Th cells. Virus transmission involves a high-affinity interaction between the DC-specific surface molecule DC-SIGN and the viral envelope glycoprotein gp120 and subsequent internalization of the virus, which remains infectious. The mechanism of viral transmission from DC to T cells is currently unknown. Sentinel immature DC (iDC) develop into Th1-promoting effector DC1 or Th2-promoting DC2, depending on the activation signals. We studied the ability of these effector DC subsets to support HIV-1 transmission in vitro. Compared with iDC, virus transmission is greatly upregulated for the DC1 subset, whereas DC2 cells are inactive. Increased transmission by DC1 correlates with increased expression of ICAM-1, and blocking studies confirm that ICAM-1 expression on DC is important for HIV transmission. The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission.

scholarly journals Activity of and Effect of Subcutaneous Treatment with the Broad-Spectrum Antiviral Lectin Griffithsin in Two Laboratory Rodent Models

2013 ◽  
Vol 58 (1) ◽  
pp. 120-127 ◽  
Author(s):  
Christopher Barton ◽  
J. Calvin Kouokam ◽  
Amanda B. Lasnik ◽  
Oded Foreman ◽  
Alexander Cambon ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Ebola Virus ◽  
Viral Infections ◽  
Antiviral Treatment ◽  
Enveloped Viruses ◽  
Minimal Toxicity ◽  
Human T Cell ◽  
Long Term Treatment ◽  
Hiv 1

ABSTRACTGriffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.

scholarly journals Polymorphisms in interferon regulatory factor 7 reduce interferon-α responses of plasmacytoid dendritic cells to HIV-1

AIDS ◽  
2011 ◽  
Vol 25 (5) ◽  
pp. 715-717 ◽  
Author(s):  
Judy Chang ◽  
Robert J Lindsay ◽  
Smita Kulkarni ◽  
Jeffrey D Lifson ◽  
Mary Carrington ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Interferon Regulatory Factor ◽  
Plasmacytoid Dendritic Cells ◽  
Interferon Α ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 7 ◽  
Hiv 1

scholarly journals Neisseria gonorrhoeae effectively blocks HIV-1 replication by eliciting a potent TLR9-dependent interferon-α response from plasmacytoid dendritic cells

2010 ◽  
Vol 12 (12) ◽  
pp. 1703-1717 ◽  
Author(s):  
Wendy N. Dobson-Belaire ◽  
Anuradha Rebbapragada ◽  
Rebecca J. Malott ◽  
Feng Yun Yue ◽  
Colin Kovacs ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Neisseria Gonorrhoeae ◽  
Plasmacytoid Dendritic Cells ◽  
Interferon Α ◽  
Hiv 1

Loss of blood CD11c+ myeloid and CD11c−plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load

Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2574-2576 ◽  
Author(s):  
Heather Donaghy ◽  
Anton Pozniak ◽  
Brian Gazzard ◽  
Nad Qazi ◽  
Jill Gilmour ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Rna Virus ◽  
Interferon Α ◽  
Lymphoid Tissues ◽  
Virus Load ◽  
Cell Responses ◽  
Plasma Virus Load ◽  
Antigen Presenting ◽  
Hiv 1

Abstract Human blood contains at least 2 subpopulations of antigen-presenting dendritic cells (DCs) that can be differentiated by their expression of CD11c. Myeloid DCs (myDCs), which are CD11c+, trap invading pathogens in the tissues and then migrate to lymphoid tissues where they stimulate pathogen-specific T-cell responses. Plasmacytoid DCs (pcDCs), which are CD11c−, secrete interferon-α in response to viral infections. This study reports that in HIV-1 infection there is a progressive depletion of both these DC populations and that this correlates with an increasing HIV-1 plasma virus load. The median numbers of myDCs and pcDCs were 6978/mL and 9299/mL, respectively, in healthy male controls and 2298/mL and 1640/mL, respectively, in patients with more than 105 HIV-1 RNA copies/mL. Both DC populations expressed CD4, CCR5, and CXCR4. The findings suggest that loss of DCs in HIV infection may contribute to disease progression.

Experiences on antiviral treatment for chronic viral B and C hepatitis patients in Hungary. 1998–2004

2007 ◽  
Vol 148 (18) ◽  
pp. 819-826 ◽  
Author(s):  
Alajos Pár ◽  
István Tornai ◽  
Ferenc Szalay
Keyword(s):  
Hepatitis C ◽  
Antiviral Treatment ◽  
Interferon Α ◽  
Standard Interferon

Az utolsó évtizedben számos multicentrikus, randomizált vizsgálat bizonyította az előrehaladást a krónikus vírushepatitisek kezelésében. Ugyanakkor csak korlátozott számú és ellentmondásos adatokat közöltek az antivirális terápia reális értékéről a mindennapos rutin klinikai gyakorlatában. Cél: Retrospektív felmérést végeztünk a terápia hatékonyságának megállapítására krónikus B- és C-hepatitisben, egy 7 éves periódus alatt kezelt országos populációban. Emellett bemutatjuk még egy hazai prospektív vizsgálat néhány adatát is. Módszerek: 220 krónikus B-hepatitises beteget kezeltünk, közülük 112 standard interferon-, 23 pegilált interferon-, 85 lamivudin-terápiában részesült, akikben a HbeAg-szerokonverzió és/vagy HBV-DNS-negatívvá válás arányát vizsgáltuk. A retrospektív elemzésben szereplő 2442 krónikus C-hepatitises közül 333 standard interferon-monoterápiát, 1122 standard interferon + ribavirin kombinációt és 987 pegilált interferon + ribavirin-kezelést kapott. A prospektív vizsgálatban 69 HCV1-beteg pegilált interferon α-2a + ribavirin terápiában részesült 6–12 hónapon át. A tartós virológiai válasz mellett vizsgáltuk a kedvező kimenetel prediktorait és a mellékhatások előfordulását. Eredmények: Krónikus B-hepatitisben a standard interferon 31%-os, a pegilált interferon 30%-os, a lamivudin 31–33%-os tartós vírusnegativitáshoz vezetett. Krónikus C-hepatitisben a tartós virológiai válasz aránya az interferon-monoterápiával észlelt 13%-ról a pegilált interferon + ribavirin mellett 31%-ra nőtt, a prospektív vizsgálatban ez 48% volt. A jó prognózis prediktora a rapid (4 hetes) és a korai (12 hetes) virológiai válasz, a női nem, az életkor, BMI és az adherencia volt. A betegek 9%-ában fordult elő mellékhatás, leggyakrabban cytopenia, haemolysis és depresszió. Következtetés: A krónikus B-hepatitisszel ellentétben, a hepatitis C-vírusinfekció kezelésének effektivitása hazánkban is fokozatosan javult. A mindennapi gyakorlat országos adatai azonban elmaradnak a prospektív vizsgálat sikerességétől. A jövőben hatékonyabb terápiás stratégiák szükségesek, beleértve az individualizált dozírozást és az új antivirális szerek alkalmazását.

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