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Multifaceted roles for STAT3 in gammaherpesvirus latency revealed through in vivo B cell knockout models

  1. Author:
    Hogan, Chad H
    Owens, Shana M
    Reynoso, Glennys V
    Liao, Yifei
    Meyer,Thomas
    Zelazowska, Monika A
    Liu, Bin
    Li, Xiaofan
    Grosskopf, Anna K [ORCID]
    Khairallah, Camille
    Kirillov, Varvara
    Reich, Nancy C
    Sheridan, Brian S
    McBride, Kevin M [ORCID]
    Gewurz, Benjamin E
    Hickman, Heather D [ORCID]
    Forrest, J Craig
    Krug, Laurie T [ORCID]

  2. Author Address

    Graduate Program in Genetics, Stony Brook University, Stony Brook, New York, USA., HIV & AIDS Malignancy Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA., Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA., Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Division of Infectious Disease, Department of Medicine, Brigham and Women 39;s Hospital, Harvard Medical School, Boston, Massachusetts, USA., CCR Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York, USA., Harvard Program in Virology, Harvard Medical School, Boston, Massachusetts, USA., Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA., Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.,
    1. Year: 2024
    2. Date: Jan 03
    3. Epub Date: 2024 01 03
  2. Journal: mBio
    1. Pages: e0299823
  4. Type of Article: Article
  5. Article Number: e0299823
  1. Abstract:

    There are no directed therapies to the latency program of the human gammaherpesviruses, Epstein-Barr virus and Kaposi sarcoma herpesvirus. Activated host factor signal transducer and activator of transcription 3 (STAT3) is a hallmark of cancers caused by these viruses. We applied the murine gammaherpesvirus pathogen system to explore STAT3 function upon primary B cell infection in the host. Since STAT3 deletion in all CD19+ B cells of infected mice led to altered B and T cell responses, we generated chimeric mice with both normal and STAT3-deleted B cells. B cells lacking STAT3 failed to support virus latency compared to normal B cells from the same infected animal. Loss of STAT3 impaired B cell proliferation and differentiation and led to a striking upregulation of interferon-stimulated genes. These findings expand our understanding of STAT3-dependent processes that are key to its function as a pro-viral latency determinant for oncogenic gammaherpesviruses in B cells and may provide novel therapeutic targets.

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External Sources

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  2. DOI: 10.1128/mbio.02998-23
  3. PMID: 38170993

Library Notes

  1. Fiscal Year: FY2023-2024
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