PMID- 36451809
OWN - NLM
STAT- MEDLINE
DCOM- 20221202
LR  - 20240124
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - A minimally-edited mouse model for infection with multiple SARS-CoV-2 strains.
PG  - 1007080
LID - 10.3389/fimmu.2022.1007080 [doi]
LID - 1007080
AB  - Efficient mouse models to study SARS-CoV-2 infection are critical for the 
      development and assessment of vaccines and therapeutic approaches to mitigate the 
      current pandemic and prevent reemergence of COVID-19. While the first generation 
      of mouse models allowed SARS-CoV-2 infection and pathogenesis, they relied on 
      ectopic expression and non-physiological levels of human angiotensin-converting 
      enzyme 2 (hACE2). Here we generated a mouse model carrying the minimal set of 
      modifications necessary for productive infection with multiple strains of 
      SARS-CoV-2. Substitution of only three amino acids in the otherwise native mouse 
      Ace2 locus (Ace2 (TripleMutant) or Ace2), was sufficient to render mice 
      susceptible to both SARS-CoV-2 strains USA-WA1/2020 and B.1.1.529 (Omicron). 
      Infected Ace2 mice exhibited weight loss and lung damage and inflammation, 
      similar to COVID-19 patients. Previous exposure to USA-WA1/2020 or mRNA 
      vaccination generated memory B cells that participated in plasmablast responses 
      during breakthrough B.1.1.529 infection. Thus, the Ace2 mouse replicates human 
      disease after SARS-CoV-2 infection and provides a tool to study immune responses 
      to sequential infections in mice.
CI  - Copyright (c) 2022 Nakandakari-Higa, Parsa, Reis, de Carvalho, Mesin, Hoffmann, 
      Bortolatto, Muramatsu, Lin, Bilate, Rice, Pardi, Mucida, Victora and Canesso.
FAU - Nakandakari-Higa, Sandra
AU  - Nakandakari-Higa S
AD  - Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, 
      United States.
FAU - Parsa, Roham
AU  - Parsa R
AD  - Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, 
      United States.
FAU - Reis, Bernardo S
AU  - Reis BS
AD  - Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, 
      United States.
FAU - de Carvalho, Renan V H
AU  - de Carvalho RVH
AD  - Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, 
      United States.
FAU - Mesin, Luka
AU  - Mesin L
AD  - Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, 
      United States.
FAU - Hoffmann, Hans-Heinrich
AU  - Hoffmann HH
AD  - Laboratory of Virology and Infectious Disease, The Rockefeller University, New 
      York, NY, United States.
FAU - Bortolatto, Juliana
AU  - Bortolatto J
AD  - Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, 
      United States.
AD  - Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, 
      United States.
FAU - Muramatsu, Hiromi
AU  - Muramatsu H
AD  - Department of Microbiology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, United States.
FAU - Lin, Paulo J C
AU  - Lin PJC
AD  - Acuitas Therapeutics, Vancouver, BC, Canada.
FAU - Bilate, Angelina M
AU  - Bilate AM
AD  - Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, 
      United States.
FAU - Rice, Charles M
AU  - Rice CM
AD  - Laboratory of Virology and Infectious Disease, The Rockefeller University, New 
      York, NY, United States.
FAU - Pardi, Norbert
AU  - Pardi N
AD  - Department of Microbiology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA, United States.
FAU - Mucida, Daniel
AU  - Mucida D
AD  - Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, 
      United States.
AD  - Howard Hughes Medical Institute, The Rockefeller University, New York, NY, United 
      States.
FAU - Victora, Gabriel D
AU  - Victora GD
AD  - Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, 
      United States.
FAU - Canesso, Maria Cecilia C
AU  - Canesso MCC
AD  - Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, 
      United States.
AD  - Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, 
      United States.
LA  - eng
GR  - P01 AI165075/AI/NIAID NIH HHS/United States
GR  - R01 AI153064/AI/NIAID NIH HHS/United States
GR  - R01 AI146101/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221114
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *SARS-CoV-2
MH  - Angiotensin-Converting Enzyme 2/genetics
MH  - *COVID-19
MH  - Disease Models, Animal
MH  - Pandemics
PMC - PMC9703079
OTO - NOTNLM
OT  - SARS-CoV-2
OT  - lung inflammation
OT  - mRNA vaccine
OT  - memory B cells
OT  - mouse ACE2
COIS- NP is named on a patent describing the use of nucleoside-modified mRNA in lipid 
      nanoparticles as a vaccine platform. He has disclosed those interests fully to 
      the University of Pennsylvania and has an approved plan in place for managing any 
      potential conflicts arising from the licensing of that patent. PJCL is an 
      employee of Acuitas Therapeutics, a company involved in the development of 
      mRNA-LNP therapeutics. GDV is a scientific advisor for Vaccine Company, Inc. The 
      remaining authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/12/02 06:00
MHDA- 2022/12/03 06:00
PMCR- 2022/11/14
CRDT- 2022/12/01 02:29
PHST- 2022/07/29 00:00 [received]
PHST- 2022/10/24 00:00 [accepted]
PHST- 2022/12/01 02:29 [entrez]
PHST- 2022/12/02 06:00 [pubmed]
PHST- 2022/12/03 06:00 [medline]
PHST- 2022/11/14 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.1007080 [doi]
PST - epublish
SO  - Front Immunol. 2022 Nov 14;13:1007080. doi: 10.3389/fimmu.2022.1007080. 
      eCollection 2022.