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.