title: 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.
authors.affiliation: Departamento de Química Biológica, Facultad Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Guiraldes 2160, Ciudad Universitaria Pabellón II. 4° piso, C1428EGA Buenos Aires, Argentina.
authors.forename: María Guadalupe
authors.initials: MG
authors.lastname: Martínez
authors.forename: Mariano
authors.initials: M
authors.lastname: Prado Acosta
authors.forename: Nélida A
authors.initials: NA
authors.lastname: Candurra
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Ruzal
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001117:Arenaviridae Infections; D001426:Bacterial Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D016384:Consensus Sequence; D018051:Junin virus / Q000187:drug effects*; D007779:Lactobacillus acidophilus; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D053586:Virus Internalization / Q000187:drug effects*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000998:Antiviral Agents; D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C055764:S-layer proteins; C070683:surface layer protein A, Bacteria