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S-layer proteins of Lactobacillus acidophilus inhibits JUNV infection.

Abstract
It has been previously described that S-layer binds to the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209). It was also shown that DC-SIGN is a cell-surface adhesion factor that enhances viral entry of several virus families. Among those, Junin virus (JUNV) entry is enhanced in cells expressing DC-SIGN and for that reason surface-layer protein (S-layer) of Lactobacillus acidophilus ATCC 4365 was evaluated as a possible JUNV inhibitor. Experiments using 3T3 cells stably expressing DC-SIGN, showed an almost complete inhibition of JUNV infection when they were treated with S-layer in a similar extend as the inhibition shown by mannan. However no inhibition effect was observed in 3T3 wild type cells or in 3T3 cells expressing liver/lymph node-specific ICAM-3 grabbing nonintegrin (L-SIGN or DC-SIGNR or CD209L). Treatments with S-layer during different times in the infection demonstrated that inhibition was only observed when S-layer was presented in early stages of the viral infection. This inhibition does not involve the classic recognition of mannose by this C-type lectin as the S-layer showed no evidence to be glycosylated. In fact, the highly basic nature of the S-layer (pI>9.5) seems to be involved in electrostatic interactions between DC-SIGN and S-layer, since high pH abolished the inhibitory effect on infection cause by the S-layer. In silico analysis predicts a Ca(2+)-dependant carbohydrate recognition domain in the SlpA protein. This novel characteristic of the S-layer, a GRAS status protein, contribute to the pathogen exclusion reported for this probiotic strain and may be applied as an antiviral agent to inhibit several kinds of viruses.
AuthorsMaría Guadalupe Martínez, Mariano Prado Acosta, Nélida A Candurra, Sandra M Ruzal
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 422 Issue 4 Pg. 590-5 (Jun 15 2012) ISSN: 1090-2104 [Electronic] United States
PMID22595457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Inc. All rights reserved.
Chemical References
  • Antiviral Agents
  • Bacterial Proteins
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • S-layer proteins
  • surface layer protein A, Bacteria
Topics
  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Antiviral Agents (chemistry, isolation & purification, pharmacology)
  • Arenaviridae Infections
  • Bacterial Proteins (isolation & purification, pharmacology)
  • Cell Adhesion Molecules (genetics, metabolism)
  • Chlorocebus aethiops
  • Consensus Sequence
  • Junin virus (drug effects)
  • Lactobacillus acidophilus
  • Lectins, C-Type (genetics, metabolism)
  • Membrane Glycoproteins (chemistry, isolation & purification, pharmacology)
  • Mice
  • Molecular Sequence Data
  • Receptors, Cell Surface (genetics, metabolism)
  • Vero Cells
  • Virus Internalization (drug effects)

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