Perinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells

Carmen Rožmanić, Berislav Lisnić, Marina Pribanić Matešić, Andrea Mihalić, Lea Hiršl, Eugene Park, Ana Lesac Brizić, Daniela Indenbirken, Ina Viduka, Marina Šantić, Barbara Adler, Wayne M. Yokoyama, Astrid Krmpotić, Vanda Juranić Lisnić, Stipan Jonjić () and Ilija Brizić ()
Additional contact information
Carmen Rožmanić: University of Rijeka
Berislav Lisnić: University of Rijeka
Marina Pribanić Matešić: University of Rijeka
Andrea Mihalić: University of Rijeka
Lea Hiršl: University of Rijeka
Eugene Park: Washington University School of Medicine
Ana Lesac Brizić: University of Rijeka
Daniela Indenbirken: Heinrich Pette Institute, Leibniz Institute for Experimental Virology
Ina Viduka: University of Rijeka, Faculty of Medicine
Marina Šantić: University of Rijeka, Faculty of Medicine
Barbara Adler: Max von Pettenkofer Institute & Gene Center, Virology, Faculty of Medicine, LMU Munich
Wayne M. Yokoyama: Washington University School of Medicine
Astrid Krmpotić: Faculty of Medicine, University of Rijeka
Vanda Juranić Lisnić: University of Rijeka
Stipan Jonjić: University of Rijeka
Ilija Brizić: University of Rijeka

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Infections in early life can elicit substantially different immune responses and pathogenesis than infections in adulthood. Here, we investigate the consequences of murine cytomegalovirus infection in newborn mice on NK cells. We show that infection severely compromised NK cell maturation and functionality in newborns. This effect was not due to compromised virus control. Inflammatory responses to infection dysregulated the expression of major transcription factors governing NK cell fate, such as Eomes, resulting in impaired NK cell function. Most prominently, NK cells from perinatally infected mice have a diminished ability to produce IFN-γ due to the downregulation of long non-coding RNA Ifng-as1 expression. Moreover, the bone marrow’s capacity to efficiently generate new NK cells is reduced, explaining the prolonged negative effects of perinatal infection on NK cells. This study demonstrates that viral infections in early life can profoundly impact NK cell biology, including long-lasting impairment in NK cell functionality.

Date: 2023
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DOI: 10.1038/s41467-023-42182-w

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