Binding of DC-SIGN to the Hemagglutinin of Influenza A Viruses Supports Virus Replication in DC-SIGN Expressing Cells

Hillaire, Marine L. B.; Nieuwkoop, Nella J.; Boon, Adrianus C. M.; Mutsert, Gerrie de; Trierum, Stella E. Vogelzang-van; Fouchier, Ron A. M.; Osterhaus, Albert D. M. E.; Rimmelzwaan, Guus F.

doi:10.1371/journal.pone.0056164

Cited by 46 publications

(48 citation statements)

References 43 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although ␣2,3-or ␣2,6-linked sialic acid is considered the main IAV receptor and a key determinant for host and tissue tropism (44)(45)(46), sialidated-protein receptors are generally thought to facilitate virus entry (13). However, several lectin-type receptors (i.e., galactose-type lectin, mannose receptor, and DC-SIGN) that appear to bind IAV independently of sialic acid have been identified (47)(48)(49)(50). Accordingly, influenza virus can use multiple endocytic pathways to gain entry into host cells (7)(8)(9)11).…”

Section: Discussionmentioning

confidence: 99%

Novel Roles of Focal Adhesion Kinase in Cytoplasmic Entry and Replication of Influenza A Viruses

Elbahesh

Cline

Baranovich

et al. 2014

J Virol

View full text Add to dashboard Cite

Viruses IMPORTANCEWe found that FAK links early activation of PI3K and actin reorganization, thereby regulating influenza virus entry. Surprisingly, we also found that FAK can regulate viral RNA replication independently of its role in entry. Our study addresses a knowledge gap in the understanding of signaling events triggered by influenza virus that mediate its internalization and initiation of the infection cycle. Understanding of these fundamental molecular events will be necessary to identify novel host targets, such as FAK, and development of future anti-influenza virus therapeutics.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel Roles of Focal Adhesion Kinase in Cytoplasmic Entry and Replication of Influenza A Viruses

Elbahesh

Cline

Baranovich

et al. 2014

J Virol

View full text Add to dashboard Cite

show abstract

“…DC‐SIGN expressed in Lec2 Chinese hamster ovary (CHO) cells (glycosylation mutant deficient in CMP‐sialic acid transport) was shown to be an alternative receptor for glycans on the hemagglutinin (HA) of seasonal influenza A virus (H3N2) and A/PR/8/34 (PR8, H1N1) . Although, Hillaire et al have suggested that DC‐SIGN is a receptor of the A (H1N1) pdm09 subtype (A/Netherlands/602/09) , definitive evidence for the same is still awaited.…”

mentioning

confidence: 99%

High doses of recombinant mannan‐binding lectin inhibit the binding of influenza A(H1N1)pdm09 virus with cells expressing DC‐SIGN

Shang

Tao

et al. 2017

APMIS

View full text Add to dashboard Cite

The pandemic influenza A (H1N1)pdm09 virus continues to be a threat to human health. Low doses of mannan-binding lectin (MBL) (<1 μg/mL) were shown not to protect against influenza A(H1N1)pdm09 infection. However, the effect of high doses of MBL has not been investigated. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) has been proposed as an alternative receptor for influenza A(H1N1)pdm09 virus. In this study, we examined the expression of DC-SIGN on DCs as well as on acute monocytic leukemia cell line, THP-1. High doses of recombinant or human MBL inhibited binding of influenza A(H1N1)pdm09 to both these cell types in the presence of complement derived from bovine serum. Further, anti-DC-SIGN monoclonal antibody inhibited binding of influenza A(H1N1)pdm09 to both DC-SIGN-expressing DCs and THP-1 cells. This study demonstrates that high doses of MBL can inhibit binding of influenza A(H1N1)pdm09 virus to DC-SIGN-expressing cells in the presence of complement. Our results suggest that DC-SIGN may be an alternative receptor for influenza A(H1N1)pdm09 virus.

show abstract

“…CHO-ctrl, Lec2-ctrl, Lec2-Lg, Lec2-Lg P23I, and Lec2-⌬Lg cells (5 ϫ 10 4 cells/250 l) were seeded into eight-well chamber slides (Lab-Tek, Nunc, Denmark), cultured overnight, and infected with 10 7 PFU of IAV (corresponding to a multiplicity of infection [MOI] of 80), and the percentage of IAV-infected cells was determined as described previously (5,6,9). Briefly, after overnight culture, cell monolayers were washed and incubated with IAV or RSV in serum-free medium for 1 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…The macrophage mannose receptor (MMR) and macrophage ga-lactose-type lectin (MGL) have been implicated as receptors for infectious entry of IAV into murine M (5-7), and human DC-SIGN has been reported to bind to IAV, resulting in enhanced infection of host cells (8)(9)(10). MMR, MGL, and DC-SIGN are C-type lectin receptors (CLRs) that express a conserved carbohydrate recognition domain that binds to derivatives of mannose (for MMR and DC-SIGN) or galactose (for MGL), and these sugars are commonly expressed on the surface of a range of pathogens, including viruses (11).…”

mentioning

confidence: 99%

The C-type Lectin Langerin Functions as a Receptor for Attachment and Infectious Entry of Influenza A Virus

Londrigan

Nasr

et al. 2016

J Virol

View full text Add to dashboard Cite

It is well established that influenza A virus (IAV) attachment to and infection of epithelial cells is dependent on sialic acid (SIA)at the cell surface, although the specific receptors that mediate IAV entry have not been defined and multiple receptors may exist. Lec2 Chinese hamster ovary (CHO) cells are SIA deficient and resistant to IAV infection. Here we demonstrate that the expression of the C-type lectin receptor langerin in Lec2 cells (Lec2-Lg) rendered them permissive to IAV infection, as measured by replication of the viral genome, transcription of viral mRNA, and synthesis of viral proteins. Unlike SIA-dependent infection of parental CHO cells, IAV attachment and infection of Lec2-Lg cells was mediated via lectin-mediated recognition of mannoserich glycans expressed by the viral hemagglutinin glycoprotein. Lec2 cells expressing endocytosis-defective langerin bound IAV efficiently but remained resistant to IAV infection, confirming that internalization via langerin was essential for infectious entry. Langerin-mediated infection of Lec2-Lg cells was pH and dynamin dependent, occurred via clathrin-and caveolin-mediated endocytic pathways, and utilized early (Rab5 ؉ ) but not late (Rab7 ؉ ) endosomes. This study is the first to demonstrate that langerin represents an authentic receptor that binds and internalizes IAV to facilitate infection. Moreover, it describes a unique experimental system to probe specific pathways and compartments involved in infectious entry following recognition of IAV by a single cell surface receptor. IMPORTANCE On the surface of host cells, sialic acid (SIA) functions as the major attachment factor for influenza A viruses (IAV). However, few studies have identified specific transmembrane receptors that bind and internalize IAV to facilitate infection. Here we identify human langerin as a transmembrane glycoprotein that can act as an attachment factor and a bone fide endocytic receptor for IAV infection. Expression of langerin by an SIA-deficient cell line resistant to IAV rendered cells permissive to infection. As langerin represented the sole receptor for IAV infection in this system, we have defined the pathways and compartments involved in infectious entry of IAV into cells following recognition by langerin. Influenza A viruses (IAV) enter and infect cells in a pH-dependent manner. In humans, epithelial cells lining the respiratory tract are the primary targets of IAV infection and support productive replication, resulting in virus amplification and spread. Seasonal IAV also infect airway macrophages (M) and dendritic cells (DC), generally resulting in abortive replication, although virulent strains such as highly pathogenic avian influenza can replicate productively in these cells (reviewed in reference 1).It is generally accepted that binding of the IAV hemagglutinin (HA) to sialic acid (SIA) residues expressed at the cell surface is the first step in initiating infectious entry; however, binding to SIA residues per se does not induce virus internalization. Rather,...

show abstract

Binding of DC-SIGN to the Hemagglutinin of Influenza A Viruses Supports Virus Replication in DC-SIGN Expressing Cells

Cited by 46 publications

References 43 publications

Novel Roles of Focal Adhesion Kinase in Cytoplasmic Entry and Replication of Influenza A Viruses

Novel Roles of Focal Adhesion Kinase in Cytoplasmic Entry and Replication of Influenza A Viruses

High doses of recombinant mannan‐binding lectin inhibit the binding of influenza A(H1N1)pdm09 virus with cells expressing DC‐SIGN

The C-type Lectin Langerin Functions as a Receptor for Attachment and Infectious Entry of Influenza A Virus

Contact Info

Product

Resources

About