UBXN3B Restricts Viral Pathogenesis by Maintaining Hematopoietic Homeostasis

WANG, P.; Geng, T.; Yang, D.; Lin, T.; Harrison, A.; Haynes, L.; Torrance, B.; Wang, B.; Vella, A. T.; Cheng, G.; Fikrig, E.; Yang, L.

doi:10.1101/2021.03.04.433919

bioRxiv · 10.1101/2021.03.04.433919

UBXN3B Restricts Viral Pathogenesis by Maintaining Hematopoietic Homeostasis

WANG, P.·Geng, T.·Yang, D.·Lin, T.·Harrison, A.·Haynes, L.·Torrance, B.·Wang, B.·Vella, A. T.·Cheng, G.·Fikrig, E.·Yang, L.

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Abstract

Hematopoiesis is finely regulated to enable timely production of the right numbers and types of mature immune cells to maintain tissue homeostasis. Dysregulated hematopoiesis may compromise antiviral immunity and/or exacerbate immunopathogenesis. Herein, we report an essential role of UBXN3B in maintenance of hematopoietic homeostasis and restriction of immunopathogenesis during respiratory viral infection. Ubxn3b deficient (Ubxn3b-/-) mice are highly vulnerable to SARS-CoV-2 and influenza A infection, characterized by more severe lung immunopathology, lower virus-specific IgG, significantly fewer B cells, but more myeloid cells than Ubxn3b+/+ littermates. This aberrant immune compartmentalization is recapitulated in uninfected Ubxn3b-/- mice. Mechanistically, UBXN3B controls precursor B-I (pre-BI) transition to pre-BII and subsequent proliferation in a cell-intrinsic manner, by maintaining BLNK protein stability and pre-BCR signaling. These results reveal an essential role of UBXN3B for the early stage of B cell development.

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WANG, P., Geng, T., Yang, D., Lin, T., Harrison, A., Haynes, L., Torrance, B., Wang, B., Vella, A. T., Cheng, G., Fikrig, E., Yang, L.. 2021-03-04. UBXN3B Restricts Viral Pathogenesis by Maintaining Hematopoietic Homeostasis. https://doi.org/10.1101/2021.03.04.433919

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