{
  "abstract": "Viruses rely on coordinated host pathways to exit the cell and propagate infection. We have come to appreciate that non-enveloped enteric viruses can use both lytic and non-lytic strategies to exit host cells. However, it remains unclear how astroviruses, a major causative agent of pediatric diarrhea, facilitate this final step in their replication cycle. Because astroviruses infect small intestinal goblet cells, we investigated whether mucus secretion could enable a pathway of non-lytic viral egress. Using the murine astrovirus model, we found that virus release co-occurred almost exclusively with mucus secretion from goblet cells. At the tissue level, mucus secretion also correlated with infection kinetics, characterized by a return to baseline secretion during viral clearance. Further, disruption of mucin biosynthesis reduced viral shedding, and stimulating mucus secretion with carbachol increased viral release. To examine this pathway with human astrovirus, we established a new infection model in LS174T goblet cells. We observed that human astrovirus colocalized with MUC2 within the cell and with purified mucin granules. Stimulating cells with carbachol enhanced mucus and virus release, which could be blocked by the addition of a muscarinic receptor antagonist. Further, we found that blocking intracellular calcium, which drives mucin granule exocytosis, also reduced virus release. Together, these findings demonstrate that mucus secretion is a novel form of non-lytic enteric viral egress, which deepens our understanding of the astrovirus replication cycle and may hold clues to understanding its pathogenesis. Author summary: Astroviruses cause pediatric diarrhea worldwide, yet we understand little about how they replicate inside a cell and cause disease. Human and murine astroviruses infect goblet cells, which are the main mucus producers in the intestine. Here, we use both mouse models and human cell culture models to examine whether mucus secretion enables a pathway for astrovirus to exit from goblet cells and spread. When we blocked mucus secretion, we observed reduced virus released. Conversely, when we stimulated mucus secretion, we observed increased virus release. We also found that subcellular structures that package mucus co-isolated with virus particles. This discovery identifies a unique exit strategy for an enteric virus that allows it to spread without having to bust open and kill its host cell. Understanding this host-virus interaction during the replication cycle can provide new insights into pathogenesis and potentially new targets for treatments strategies that prevent astrovirus spread.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, United States of America."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Natalie Pedicino"
    },
    {
      "affs": [
        0
      ],
      "name": "Melanie G Kirkpatrick"
    },
    {
      "affs": [
        0
      ],
      "name": "Michelle Ann Pablo"
    },
    {
      "affs": [
        0
      ],
      "name": "Jacob Gulman"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicole Heredia-Osuna"
    },
    {
      "affs": [
        0
      ],
      "name": "Valerie Cortez",
      "orcid": "0000-0002-1267-5596"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5nk5m52zq6zd0.bib",
  "cited_by": 1,
  "doi": "10.1371/journal.ppat.1014683",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014683",
  "id": "5nk5m52zq6zd0",
  "issns": [
    "1553-7374",
    "1553-7366"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014683",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|Viral gastroenteritis research and epidemiology"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Body fluids/Mucus"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Mucin"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Astroviruses"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Virology/Viral replication/Viral packaging"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/RNA viruses/Astroviruses"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Astroviruses"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Body fluids/Mucus"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Physiological processes/Secretion"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Body fluids/Mucus"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Infectious diseases/Viral diseases/Astrovirus infection"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Astroviruses"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Mouse models"
    ],
    [
      "plos",
      "/Research and analysis methods/Biological cultures/Cell lines/Caco-2 cells"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Mouse models"
    ]
  ],
  "openalex": "W7221185623",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014683&type=printable",
  "pmcid": "PMC13671654",
  "pmid": "42853874",
  "published": "2026-10-09",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/5nk5m52zq6zd0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:30Z",
      "native_id": "10.1371/journal.ppat.1014683",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014683"
    },
    {
      "first_seen": "2026-10-30T12:18:12Z",
      "native_id": "MED:42853874",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42853874"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
    },
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "Astroviruses use mucus secretion as a novel form of viral egress",
  "title_text": "Astroviruses use mucus secretion as a novel form of viral egress",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:12Z",
  "url": "https://research.draconitic.com/paper/5nk5m52zq6zd0",
  "venue": "PLOS Pathogens",
  "versions": []
}