TY - JOUR
T1 - Characterization of SARS-CoV-2 Spike mutations important for infection of mice and escape from human immune sera
AU - PVI study group
AU - Rathnasinghe, Raveen
AU - Jangra, Sonia
AU - Ye, Chengjin
AU - Cupic, Anastasija
AU - Singh, Gagandeep
AU - Martínez-Romero, Carles
AU - Mulder, Lubbertus C.F.
AU - Kehrer, Thomas
AU - Yildiz, Soner
AU - Choi, Angela
AU - Yeung, Stephen T.
AU - Mena, Ignacio
AU - Gillespie, Virginia
AU - De Vrieze, Jana
AU - Aslam, Sadaf
AU - Stadlbauer, Daniel
AU - Meekins, David A.
AU - McDowell, Chester D.
AU - Balaraman, Velmurugan
AU - Corley, Michael J.
AU - Richt, Juergen A.
AU - De Geest, Bruno G.
AU - Miorin, Lisa
AU - Kleiner, Giulio
AU - Saksena, Miti
AU - Srivastava, Komal
AU - Gleason, Charles R.
AU - Bermúdez-González, Maria C.
AU - Beach, Katherine F.
AU - Russo, Kayla T.
AU - Sominsky, Levy A.
AU - Ferreri, Emily D.
AU - Chernet, Rachel L.
AU - Eaker, Lily Q.
AU - Salimbangon, Ashley Beathrese T.
AU - Jurczyszak, Denise
AU - Alshammary, Hala
AU - Mendez, Wanni A.
AU - Amoako, Angela A.
AU - Fabre, Shelcie
AU - Awawda, Mahmoud H.
AU - Shin, Amber S.
AU - Krammer, Florian
AU - Martinez-Sobrido, Luis
AU - Simon, Viviana
AU - García-Sastre, Adolfo
AU - Schotsaert, Michael
N1 - Funding Information:
We also thank Dr. Randy Albrecht for support with the BSL3 facility and procedures at the ISMMS as well as Richard Cadagan for excellent technical assistance. We acknowledge the Weill Cornell Medicine Microscopy & Image Analysis Core Facility for assistance and equipment support. This work was partially supported by the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C (to A.G.-S., F.K., and V.S.) and contract HHSN 272201400006 C (to J.A.R.), Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051 (to A.G.-S., F.K., and V.S.), and the generous support of the JPB foundation (to A.G.-S., F.K., and V.S.), the Open Philanthropy Project (#2020-215611) (to A.G.-S., F.K., and V.S.) and other philanthropic donations. This research was partly funded by NIH AI150355 grant to LCFM, by the Defense Advanced Research Projects Agency (HR0011-19-2-0020), by supplements to NIAID grant U19AI135972 and DoD grant W81XWH-20-1-0270, by NCI grant U54CA260560, by a Mercatus Center Fast Grant, by the generous support of JPB Foundation; by anonymous donors to A.G.-S. Funding for this study was provided through grants from the National Bio and Agro-Defense Facility (NBAF) Transition Funds from the State of Kansas, the DHS Center of Excellence for Emerging and Zoonotic Diseases (CEEZAD; contract number HSHQDC16-A-B0006), the AMP Core of the Center of Emerging and Zoonotic Infectious Diseases (CEZID) from the National Institute of General Medical Sciences (NIGMS) under award number P20GM130448, the NIAID Centers of Excellence for Influenza Research and Surveillance under contract number HHSN 272201400006 C, and the NIAID supported Center of Excellence for Influenza Research and Response (CEIRR, contract number 75N93021C00016) to J.A.R. B.G.D.G. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant N 817938). S.Y. is supported by The Swiss National Science Foundation (Early Postdoc Mobility Grant Project Id: P2GEP3_184202).
Funding Information:
The A.G.-S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, ImmunityBio, and Nanocomposix. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, and Esperovax. M.S. has licensed SARS-CoV-2 serological assays to commercial entities and has filed for patent protection for serological assays as well as SARS-CoV-2 vaccines. F.K. is listed as inventors on the pending patent applications. The F.K. laboratory has received research support from GSK, Dynavax, and Pfizer. F.K. has in the past received consulting fees from Curevac, Merck, Pfizer, and Seqirus. The J.A.R. laboratory received support from Tonix Pharmaceuticals, Xing Technologies and Zoetis, outside of the reported work. J.A.R. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections, owned by Kansas State University, KS, or the Icahn School of Medicine at Mount Sinai, New York. A provisional patent application on a “A novel 4 Amino Acid Insertion into the Spike Protein of SARS-CoV-2” was submitted by KSU in July 2020 with C.D.M., D.A.M., and J.A.R. listed as inventors. The remaining authors declare no competing interests.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Due to differences in human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially available SARS-CoV-2 isolates could not infect mice. Here we show that serial passaging of USA-WA1/2020 strain in mouse lungs results in “mouse-adapted” SARS-CoV-2 (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene. MA-SARS-CoV-2 infection causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese mice. Two mutations in the S gene associated with mouse adaptation (N501Y, H655Y) are present in SARS-CoV-2 variants of concern (VoCs). N501Y in the receptor binding domain of viruses of the B.1.1.7, B.1.351, P.1 and B.1.1.529 lineages (Alpha, Beta, Gamma and Omicron variants) is associated with high transmissibility and allows VoCs to infect wild type mice. We further show that S protein mutations of MA-SARS-CoV-2 do not affect neutralization efficiency by human convalescent and post vaccination sera.
AB - Due to differences in human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially available SARS-CoV-2 isolates could not infect mice. Here we show that serial passaging of USA-WA1/2020 strain in mouse lungs results in “mouse-adapted” SARS-CoV-2 (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene. MA-SARS-CoV-2 infection causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese mice. Two mutations in the S gene associated with mouse adaptation (N501Y, H655Y) are present in SARS-CoV-2 variants of concern (VoCs). N501Y in the receptor binding domain of viruses of the B.1.1.7, B.1.351, P.1 and B.1.1.529 lineages (Alpha, Beta, Gamma and Omicron variants) is associated with high transmissibility and allows VoCs to infect wild type mice. We further show that S protein mutations of MA-SARS-CoV-2 do not affect neutralization efficiency by human convalescent and post vaccination sera.
UR - http://www.scopus.com/inward/record.url?scp=85133648482&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-30763-0
DO - 10.1038/s41467-022-30763-0
M3 - Article
C2 - 35798721
AN - SCOPUS:85133648482
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3921
ER -