{
  "abstract": "Lactobacillus johnsonii N6.2-derived extracellular vesicles (EVs) provide protection against murine norovirus (MNV-1) both in vitro and in vivo . Within the proteins enriched in EVs, the SH3b2 domain of Sdp was shown to be sufficient to recapitulate the antiviral effects shown by EVs. In this report, we compared the effects of six SH3b domains of Sdp and identified amino acids expected to be important for interactions with host proteins. We found that SH3b2 showed the highest activity in inducing NF-ĸB/AP-1 and IRF pathways in RAW macrophage reporter cell lines. Structure-guided site-directed mutagenesis of SH3b2 revealed residues in SH3b2 potentially responsible for interactions with host proteins. SH3b2-G501D had significantly lower stimulation of NF-ĸB/AP-1 and IRF pathways. In addition, SH3b2-G501D showed reduced IL10 and Oas1 mRNA levels, resulting in an impaired MNV-1 antiviral response in RAW 264.7 cells. mCherry fusions to SH3b2-G501D confirmed that the effects observed were not related to reduced uptake into macrophages, as quantified by confocal microscopy. Additionally, the role of the C-terminal linker sequence in Sh3b2, which is absent in SH3b6, in uptake or signaling in macrophages was evaluated. It was found that deletion of the C-terminal linker (SH3b2ΔC2 treatment) resulted in reduced promoter activity, while SH3b6::C2 partially regained function through restoration of uptake in macrophages. These results indicate that the C-terminal linker plays an important role in internalization by macrophages. We propose that once internalized, SH3b2 mimics eukaryotic SH3 domains involved in signal transduction to activate the cellular innate immune response in macrophages.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Asra B. Sharjeel"
    },
    {
      "affs": [
        0
      ],
      "name": "Javier Rosero"
    },
    {
      "affs": [
        0
      ],
      "name": "Chantal Ronacher"
    },
    {
      "affs": [
        0
      ],
      "name": "Melissa K. Jones"
    },
    {
      "affs": [
        0
      ],
      "name": "Claudio F. Gonzalez"
    },
    {
      "affs": [
        0
      ],
      "name": "Graciela L. Lorca"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6rngtrqc79jzj.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1977036",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735725/",
  "id": "6rngtrqc79jzj",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1977036/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W7223171058",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1977036/pdf",
  "pmcid": "PMC13735725",
  "pmid": "42990931",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6rngtrqc79jzj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1977036",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1977036/full"
    },
    {
      "first_seen": "2026-11-09T12:21:21Z",
      "native_id": "PMC13735725",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1977036"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Extracellular vesicles in disease",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Specific residues modulate the antiviral activity of the extracellular vesicle-derived effector SH3b domain from Lactobacillus johnsonii N6.2",
  "title_text": "Specific residues modulate the antiviral activity of the extracellular vesicle-derived effector SH3b domain from Lactobacillus johnsonii N6.2",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:21Z",
  "url": "https://research.draconitic.com/paper/6rngtrqc79jzj",
  "venue": "Frontiers in Immunology",
  "versions": []
}