Cell Reports (Jul 2021)
Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell
- Maritza Puray-Chavez,
- Kyle M. LaPak,
- Travis P. Schrank,
- Jennifer L. Elliott,
- Dhaval P. Bhatt,
- Megan J. Agajanian,
- Ria Jasuja,
- Dana Q. Lawson,
- Keanu Davis,
- Paul W. Rothlauf,
- Zhuoming Liu,
- Heejoon Jo,
- Nakyung Lee,
- Kasyap Tenneti,
- Jenna E. Eschbach,
- Christian Shema Mugisha,
- Emily M. Cousins,
- Erica W. Cloer,
- Hung R. Vuong,
- Laura A. VanBlargan,
- Adam L. Bailey,
- Pavlo Gilchuk,
- James E. Crowe, Jr.,
- Michael S. Diamond,
- D. Neil Hayes,
- Sean P.J. Whelan,
- Amjad Horani,
- Steven L. Brody,
- Dennis Goldfarb,
- M. Ben Major,
- Sebla B. Kutluay
Affiliations
- Maritza Puray-Chavez
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Kyle M. LaPak
- Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Travis P. Schrank
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA; Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
- Jennifer L. Elliott
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Dhaval P. Bhatt
- Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Megan J. Agajanian
- Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Ria Jasuja
- Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Dana Q. Lawson
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Keanu Davis
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Paul W. Rothlauf
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Program in Virology, Harvard Medical School, Boston, MA, USA
- Zhuoming Liu
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Heejoon Jo
- University of Tennessee Health Science Center for Cancer Research, Department of Medicine, Division of Hematology and Oncology, University of Tennessee, Memphis, TN, USA
- Nakyung Lee
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Kasyap Tenneti
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Jenna E. Eschbach
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Christian Shema Mugisha
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Emily M. Cousins
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
- Erica W. Cloer
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
- Hung R. Vuong
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Laura A. VanBlargan
- Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA
- Adam L. Bailey
- Department of Pathology & Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Pavlo Gilchuk
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- James E. Crowe, Jr.
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Michael S. Diamond
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA
- D. Neil Hayes
- University of Tennessee Health Science Center for Cancer Research, Department of Medicine, Division of Hematology and Oncology, University of Tennessee, Memphis, TN, USA
- Sean P.J. Whelan
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Amjad Horani
- Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pediatrics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Steven L. Brody
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- Dennis Goldfarb
- Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Institute for Informatics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
- M. Ben Major
- Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Otolaryngology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Corresponding author
- Sebla B. Kutluay
- Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Corresponding author
- Journal volume & issue
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Vol. 36,
no. 2
p. 109364
Abstract
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of angiotensin-converting enzyme 2 (ACE2) expression. Remarkably, H522 infection requires the E484D S variant; viruses expressing wild-type S are not infectious. Anti-S monoclonal antibodies differentially neutralize SARS-CoV-2 E484D S in H522 cells as compared to ACE2-expressing cells. Sera from vaccinated individuals block this alternative entry mechanism, whereas convalescent sera are less effective. Although the H522 receptor remains unknown, depletion of surface heparan sulfates block H522 infection. Temporally resolved transcriptomic and proteomic profiling reveal alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type I interferon signaling. These findings establish an alternative SARS-CoV-2 host cell receptor for the E484D SARS-CoV-2 variant, which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis.
