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Volume 12
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10.3390/v12070724
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Article

STAT2 Limits Host Species Specificity of Human Metapneumovirus

by
Meredith C. Rogers
1,2,
Margot Miranda-Katz
1,
Yu Zhang
1,
Tim D. Oury
3,
Melissa B. Uccellini
4,5,
Adolfo García-Sastre
4,5,6,7 and
John V. Williams
1,8,*
1
Department of Pediatrics, University of Pittsburgh School of Medicine and UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA
2
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37212, USA
3
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
4
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
5
Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
6
Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
7
The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
8
Institute for Infection, Inflammation, and Immunity in Children (i4Kids), University of Pittsburgh, Pittsburgh, PA 15224, USA
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(7), 724; https://doi.org/10.3390/v12070724
Submission received: 3 June 2020 / Revised: 1 July 2020 / Accepted: 2 July 2020 / Published: 4 July 2020
(This article belongs to the Special Issue From RSV to hMPV: Role of Innate Immunity in Pathogenesis)
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Abstract

The host tropism of viral infection is determined by a variety of factors, from cell surface receptors to innate immune signaling. Many viruses encode proteins that interfere with host innate immune recognition in order to promote infection. STAT2 is divergent between species and therefore has a role in species restriction of some viruses. To understand the role of STAT2 in human metapneumovirus (HMPV) infection of human and murine tissues, we first infected STAT2−/− mice and found that HMPV could be serially passaged in STAT2−/−, but not WT, mice. We then used in vitro methods to show that HMPV inhibits expression of both STAT1 and STAT2 in human and primate cells, but not in mouse cells. Transfection of the murine form of STAT2 into STAT2-deficient human cells conferred resistance to STAT2 inhibition. Finally, we sought to understand the in vivo role of STAT2 by infecting hSTAT2 knock-in mice with HMPV, and found that mice had increased weight loss, inhibition of type I interferon signaling, and a Th2-polarized cytokine profile compared to WT mice. These results indicate that STAT2 is a target of HMPV in human infection, while the murine version of STAT2 restricts tropism of HMPV for murine cells and tissue.
Keywords: human metapneumovirus; STAT2; STAT1; virus tropism; innate immunity; type I interferon; acute respiratory infection human metapneumovirus; STAT2; STAT1; virus tropism; innate immunity; type I interferon; acute respiratory infection

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MDPI and ACS Style

Rogers, M.C.; Miranda-Katz, M.; Zhang, Y.; Oury, T.D.; Uccellini, M.B.; García-Sastre, A.; Williams, J.V. STAT2 Limits Host Species Specificity of Human Metapneumovirus. Viruses 2020, 12, 724. https://doi.org/10.3390/v12070724

AMA Style

Rogers MC, Miranda-Katz M, Zhang Y, Oury TD, Uccellini MB, García-Sastre A, Williams JV. STAT2 Limits Host Species Specificity of Human Metapneumovirus. Viruses. 2020; 12(7):724. https://doi.org/10.3390/v12070724

Chicago/Turabian Style

Rogers, Meredith C., Margot Miranda-Katz, Yu Zhang, Tim D. Oury, Melissa B. Uccellini, Adolfo García-Sastre, and John V. Williams. 2020. "STAT2 Limits Host Species Specificity of Human Metapneumovirus" Viruses 12, no. 7: 724. https://doi.org/10.3390/v12070724

APA Style

Rogers, M. C., Miranda-Katz, M., Zhang, Y., Oury, T. D., Uccellini, M. B., García-Sastre, A., & Williams, J. V. (2020). STAT2 Limits Host Species Specificity of Human Metapneumovirus. Viruses, 12(7), 724. https://doi.org/10.3390/v12070724

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