Emerging SARS-CoV-2 variants expand species tropism to rodents

Mice are not susceptible to wildtype SARS-CoV-2 infection. Emerging SARS-CoV-2 variants including B.1.1.7, B.1.351, P.1, and P.3 contain mutations in spike, which have been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that they may have evolved to expand species tropism to rodents. Here, we investigated the capacity of B.1.1.7 and other emerging SARS-CoV-2 variants in infecting mouse (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Our results show that B.1.1.7 and P.3, but not B.1 or wildtype SARS-CoV-2, can utilize mouse and rat ACE2 for virus entry in vitro. High infectious virus titers, abundant viral antigen expression, and pathological changes are detected in the nasal turbinate and lung of B.1.1.7-inocluated mice and rats. Together, these results reveal that the current predominant circulating SARS-CoV-2 variant, B.1.1.7, has gained the capability to expand species tropism to rodents.

[1]  Jian-Piao Cai,et al.  Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity , 2021, Science Advances.

[2]  Huanchun Chen,et al.  SARS-CoV-2 Rapidly Adapts in Aged BALB/c Mice and Induces Typical Pneumonia , 2021, Journal of Virology.

[3]  Host and viral determinants for efficient SARS-CoV-2 infection of the human lung , 2021, Nature communications.

[4]  M. Koopmans,et al.  Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans , 2020, Science.

[5]  S. Perlman,et al.  COVID-19 Treatments and Pathogenesis Including Anosmia in K18-hACE2 mice , 2020, Nature.

[6]  Lisa E. Gralinski,et al.  A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice , 2020, Cell.

[7]  N. Escriou,et al.  SARS-CoV-2 Natural Transmission from Human to Cat, Belgium, March 2020 , 2020, Emerging infectious diseases.

[8]  Z. Bu,et al.  Mouse-adapted SARS-CoV-2 replicates efficiently in the upper and lower respiratory tract of BALB/c and C57BL/6J mice , 2020, Protein & Cell.

[9]  Yan Li,et al.  Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy , 2020, Science.

[10]  S. Tong,et al.  From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo , 2020, mBio.

[11]  Jian-Piao Cai,et al.  Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-β and IFN inducer , 2020, Journal of Infection.

[12]  Hanxin Lin,et al.  Broad and Differential Animal Angiotensin-Converting Enzyme 2 Receptor Usage by SARS-CoV-2 , 2020, Journal of Virology.

[13]  D. Chu,et al.  Infection of dogs with SARS-CoV-2 , 2020, Nature.

[14]  M. Veit,et al.  Comparison of Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Binding to ACE2 Receptors from Human, Pets, Farm Animals, and Putative Intermediate Hosts , 2020, Journal of Virology.

[15]  O. Tsang,et al.  Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study , 2020, The Lancet Microbe.

[16]  Dong Yang,et al.  Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19 , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  C. Lindskog,et al.  The protein expression profile of ACE2 in human tissues , 2020, bioRxiv.

[18]  K. To,et al.  Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  E. A. Agafonova,et al.  Pathogenesis of COVID-19 , 2020, CHILD`S HEALTH.

[20]  Wenling Wang,et al.  The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice , 2020, Nature.

[21]  Kai Zhao,et al.  A pneumonia outbreak associated with a new coronavirus of probable bat origin , 2020, Nature.

[22]  S. Lo,et al.  A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster , 2020, The Lancet.

[23]  O. Tsang,et al.  Transmission of Rat Hepatitis E Virus Infection to Humans in Hong Kong: A Clinical and Epidemiological Analysis , 2020, Hepatology.

[24]  The Bronx Zoo , 2019, The Bronx.

[25]  P. Woo,et al.  Discovery of a Novel Coronavirus, China Rattus Coronavirus HKU24, from Norway Rats Supports the Murine Origin of Betacoronavirus 1 and Has Implications for the Ancestor of Betacoronavirus Lineage A , 2014, Journal of Virology.

[26]  Herman Tse,et al.  Interspecies transmission and emergence of novel viruses: lessons from bats and birds , 2013, Trends in Microbiology.

[27]  T. Mcmichael,et al.  Synanthropy of Wild Mammals as a Determinant of Emerging Infectious Diseases in the Asian–Australasian Region , 2012, EcoHealth.

[28]  David K. Meyerholz,et al.  Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus , 2006, Journal of Virology.

[29]  G. Navis,et al.  Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis , 2004, The Journal of pathology.