Tropism for ciliated cells is the dominant driver of influenza viral burst size in the human airway.

Autor:	Roach SN; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455., Shepherd FK; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455., Mickelson CK; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455., Fiege JK; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455., Thielen BK; Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455., Pross LM; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455., Sanders AE; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455., Mitchell JS; Center for Immunology, University of Minnesota, Minneapolis, MN 55455., Robertson M; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455., Fife BT; Center for Immunology, University of Minnesota, Minneapolis, MN 55455.; Department of Medicine, University of Minnesota, Minneapolis, MN 55455., Langlois RA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 30; Vol. 121 (31), pp. e2320303121. Date of Electronic Publication: 2024 Jul 15.
DOI:	10.1073/pnas.2320303121
Abstrakt:	Influenza viruses pose a significant burden on global human health. Influenza has a broad cellular tropism in the airway, but how infection of different epithelial cell types impacts replication kinetics and burden in the airways is not fully understood. Using primary human airway cultures, which recapitulate the diverse epithelial cell landscape of the human airways, we investigated the impact of cell type composition on virus tropism and replication kinetics. Cultures were highly diverse across multiple donors and 30 independent differentiation conditions and supported a range of influenza replication. Although many cell types were susceptible to influenza, ciliated and secretory cells were predominantly infected. Despite the strong tropism preference for secretory and ciliated cells, which consistently make up 75% or more of infected cells, only ciliated cells were associated with increased virus production. Surprisingly, infected secretory cells were associated with overall reduced virus output. The disparate response and contribution to influenza virus production could be due to different pro- and antiviral interferon-stimulated gene signatures between ciliated and secretory populations, which were interrogated with single-cell RNA sequencing. These data highlight the heterogeneous outcomes of influenza virus infections in the complex cellular environment of the human airway and the disparate impacts of infected cell identity on multiround burst size, even among preferentially infected cell types. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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