@article{93738446c5874e5f894bd18d4897ec19,
title = "A Secreted Viral Nonstructural Protein Determines Intestinal Norovirus Pathogenesis",
abstract = "Norovirus is an enteric virus that infects intestinal epithelial tuft cells in mice. Lee et al. discover that murine norovirus NS1 is an unconventionally secreted protein that overcomes IFN-λ-mediated norovirus control and is critical for intestinal infection in mice. Additionally, vaccination with NS1 alone confers protection, suggesting potential vaccine strategies.",
keywords = "IFN-λ, NS1, norovirus, secretion, vaccine",
author = "Sanghyun Lee and Hejun Liu and Wilen, {Craig B.} and Sychev, {Zoi E.} and Chandni Desai and Hykes, {Barry L.} and Orchard, {Robert C.} and McCune, {Broc T.} and Kim, {Ki Wook} and Nice, {Timothy J.} and Handley, {Scott A.} and Baldridge, {Megan T.} and Amarasinghe, {Gaya K.} and Virgin, {Herbert W.}",
note = "Funding Information: Dr. Virgin is an employee of and owns stock in Vir Biotechnology in San Francisco, CA, and is a founder and shareholder in Casma Therapeutics in Cambridge, MA. The work reported herein was not funded by either Vir Biotechnology or Casma Therapeutics. Washington University School of Medicine holds patents on which Dr. Virgin is an inventor that are related to murine norovirus. Washington University School of Medicine and Dr. Virgin receive income based on licensing of these patents. Funding Information: The authors would like to thank D. Kreamalmeyer for animal care and breeding and Anthony Orvedahl and the other members of the Virgin lab for manuscript review and discussion. We would also like to thank the Genome Engineering and iPSC center, the Flow Cytometry & Fluorescence Activated Cell Sorting Core Facility, the Molecular Microbiology Imaging Facility, and the Elvie L. Taylor Histology Core Facility at Washington University School of Medicine for assistance with generating KO cell lines, cell sorting, and immunohistochemistry. H.W.V. was supported by the National Institutes of Health (NIH) grant U19 AI109725 and the Crohn's and Colitis Foundation grant # 326556 . S.L. was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education ( NRF-2016R1A6A3A03012352 ). M.T.B. was supported by NIH grants K22 AI127846 , R01 AI127552 , R01 OD024917 , and R01 AI139314 and DDRCC grant P30 DK052574 . T.J.N. was supported by NIH training grant 5T32A100716334 and postdoctoral fellowships from the Cancer Research Institute and the American Cancer Society . C.B.W. was supported by NIH grant 1K08AI128043-01 . R.C.O. was supported by NIH grant R00 DK116666 . B.T.M. was supported by NCI -NIH award F31CA177194-01 . K.-W.K. was supported by NIH R37 AI049653 to G. J. Randolph. G.K.A and H.L. were supported by NIH AI120943 and AI109945 . The data from this study are tabulated in the main paper and Supplemental Information. All reagents are available from H.W.V under a material transfer agreement with Washington University. Funding Information: The authors would like to thank D. Kreamalmeyer for animal care and breeding and Anthony Orvedahl and the other members of the Virgin lab for manuscript review and discussion. We would also like to thank the Genome Engineering and iPSC center, the Flow Cytometry & Fluorescence Activated Cell Sorting Core Facility, the Molecular Microbiology Imaging Facility, and the Elvie L. Taylor Histology Core Facility at Washington University School of Medicine for assistance with generating KO cell lines, cell sorting, and immunohistochemistry. H.W.V. was supported by the National Institutes of Health (NIH) grant U19 AI109725 and the Crohn's and Colitis Foundation grant #326556. S.L. was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2016R1A6A3A03012352). M.T.B. was supported by NIH grants K22 AI127846, R01 AI127552, R01 OD024917, and R01 AI139314 and DDRCC grant P30 DK052574. T.J.N. was supported by NIH training grant 5T32A100716334 and postdoctoral fellowships from the Cancer Research Institute and the American Cancer Society. C.B.W. was supported by NIH grant 1K08AI128043-01. R.C.O. was supported by NIH grant R00 DK116666. B.T.M. was supported by NCI-NIH award F31CA177194-01. K.-W.K. was supported by NIH R37 AI049653 to G. J. Randolph. G.K.A and H.L. were supported by NIH AI120943 and AI109945. The data from this study are tabulated in the main paper and Supplemental Information. All reagents are available from H.W.V under a material transfer agreement with Washington University. Conceptualization, S.L.; Methodology, S.L. H.L. C.B.W. Z.E.S. C.D. B.L.H. K.-W.K. R.C.O. and T.J.N.; Validation, S.L. H.L. C.B.W. Z.E.S. C.D. B.L.H. and M.T.B.; Investigation, S.L.; Resources, H.L. B.T.M. T.J.N. C.D. B.L.H. and S.A.H.; Writing – Original Draft, S.L.; Writing – Review & Editing, H.L. C.B.W. K.-W.K. R.C.O. T.J.N. M.T.B. and G.K.A.; Funding Acquisition, G.K.A. and H.W.V.; Supervision, H.W.V. Dr. Virgin is an employee of and owns stock in Vir Biotechnology in San Francisco, CA, and is a founder and shareholder in Casma Therapeutics in Cambridge, MA. The work reported herein was not funded by either Vir Biotechnology or Casma Therapeutics. Washington University School of Medicine holds patents on which Dr. Virgin is an inventor that are related to murine norovirus. Washington University School of Medicine and Dr. Virgin receive income based on licensing of these patents. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = jun,
day = "12",
doi = "10.1016/j.chom.2019.04.005",
language = "English",
volume = "25",
pages = "845--857.e5",
journal = "Cell Host and Microbe",
issn = "1931-3128",
number = "6",
}