Endocytic function is critical for influenza A virus infection via DC-SIGN and L-SIGN

Sci Rep. 2016 Jan 14:6:19428. doi: 10.1038/srep19428.

Abstract

The ubiquitous presence of cell-surface sialic acid (SIA) has complicated efforts to identify specific transmembrane glycoproteins that function as bone fide entry receptors for influenza A virus (IAV) infection. The C-type lectin receptors (CLRs) DC-SIGN (CD209) and L-SIGN (CD209L) enhance IAV infection however it is not known if they act as attachment factors, passing virions to other unknown receptors for virus entry, or as authentic entry receptors for CLR-mediated virus uptake and infection. Sialic acid-deficient Lec2 Chinese Hamster Ovary (CHO) cell lines were resistant to IAV infection whereas expression of DC-SIGN/L-SIGN restored susceptibility of Lec2 cells to pH- and dynamin-dependent infection. Moreover, Lec2 cells expressing endocytosis-defective DC-SIGN/L-SIGN retained capacity to bind IAV but showed reduced susceptibility to infection. These studies confirm that DC-SIGN and L-SIGN are authentic endocytic receptors for IAV entry and infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Cricetulus
  • Dogs
  • Dynamins / metabolism
  • Endocytosis*
  • Gene Expression
  • Hydrogen-Ion Concentration
  • Influenza A virus / physiology*
  • Lectins, C-Type / chemistry
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Mutation
  • N-Acetylneuraminic Acid / metabolism
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Virus / metabolism*
  • Virus Attachment
  • Virus Internalization*

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Receptors, Virus
  • Dynamins
  • N-Acetylneuraminic Acid