ArticlePLoS pathogens2015
Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Mammary and respiratory infection of sheep with H5Nx clade 2.3.4.4b viruses with milk-mediated transmission to lambs.Science advances · 2026Article
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- Fecal and Environmental Shedding of Influenza A Virus in Brazilian Swine: Genomic Evidence of Recent Human-to-Swine Transmission.Pathogens (Basel, Switzerland) · 2025Article
- Establishment and validation of a ferret model for systemic antibiotic treatment during influenza A virus infection.Lab animal · 2025Article
- The Legacy of COVID-19 in Breast Milk: The Association of Elevated Anti-Inflammatory and Antimicrobial Proteins with Vaccination or Infection.Current issues in molecular biology · 2025Article
- The gut virome and human health: From diversity to personalized medicine.Engineering microbiology · 2025Review
- Prolactin: A Key Immunoregulator in Viral Infections and Autoimmune Diseases.International journal of endocrinology · 2025Review
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- miR-24-3p Is Antiviral Against SARS-CoV-2 by Downregulating Critical Host Entry Factors.Viruses · 2024Article
- Avian Influenza Virus A(H5Nx) and Prepandemic Candidate Vaccines: State of the Art.International journal of molecular sciences · 2024Review
- Could H5N1 bird flu virus be the cause of the next human pandemic?Frontiers in microbiology · 2024Article
- Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2.Nature communications · 2023Article
- microRNA-185 Inhibits SARS-CoV-2 Infection through the Modulation of the Host's Lipid Microenvironment.Viruses · 2023Article
- After the virus has cleared-Can preclinical models be employed for Long COVID research?PLoS pathogens · 2022Review
- Human Breast Milk: From Food to Active Immune Response With Disease Protection in Infants and Mothers.Frontiers in immunology · 2022Review
- Serological Responses to Influenza Vaccination during Pregnancy.Microorganisms · 2021Review
- Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets.Scientific reports · 2021Article
- Review
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.