Abstract
COVID-19 is identified as a zoonotic disease caused by SARS-CoV-2, which also can cross-transmit to many animals but not mice. Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection. Although neither is the natural situation, they are currently utilized to establish mouse infection models. Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice. The SARS-CoV-2 (B.1.351) replicated efficiently and induced significant pathological changes in lungs and tracheas, accompanied by elevated proinflammatory cytokines in the lungs and sera. Mechanistically, the receptor-binding domain (RBD) of SARS-CoV-2 (B.1.351) spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2 (mACE2), allowing the mice highly susceptible to SARS-CoV-2 (B.1.351) infection. Our work suggests that SARS-CoV-2 (B.1.351) expands the host range and therefore increases its transmission route without adapted mutation. As the wild house mice live with human populations quite closely, this possible transmission route could be potentially risky. In addition, because SARS-CoV-2 (B.1.351) is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated, the SARS-CoV-2 (B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.
Highlights
One year and a half have passed since the initial report of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the coronavirus disease 2019 (COVID-19) pandemic still persists worldwide.[1]
We found that B.1.351 viruses replicated efficiently in expression was more significant for B.1.351 variant (p = 0.0066 for lung and trachea tissues of both BALB/c and C57BL/6 mice besides medium mouse angiotensin-converting enzyme 2 (mACE2) expression group, p < 0.0001 for high mACE2 human angiotensin-converting enzyme 2 (hACE2) mice (Fig. 3a, b)
We found that many cytokines messenger RNAs, including Il1b, Il5, Il6, Il10, Il12a/Il12p70, Ifng, Ccl[4], Ccl[5], Tnfa, Gcsf, Cxcl[1], Il1a, and Il3, were significantly induced upon B.1.351 infection in the lungs of hACE2 transgenic, BALB/c, and C57BL/6 mice (Fig. 4a–c and Supplementary Table 1)
Summary
One year and a half have passed since the initial report of the severe acute respiratory syndrome coronavirus 2 The infection of SARS-CoV-2 constant (KD) ranging from 1.16 to 31.40 nM), whereas the RBD (B.1.351) upon the wild-type mice exhibits a new transmission or S1 proteins of D614 and G614 variants showed no binding route It provides an animal model for studying affinities to mACE2, which was consistent with the previous. B HEK293T-hACE2 and HEK293T-mACE2 cells were incubated with different pseudotyped SARS-CoV-2 viruses, followed by detecting the expression of luciferase at 48 h post infection. We detected high numbers of viral RNA copies and significant pathological changes in the trachea, which was consistent with the previous finding that both human lungs and airways epithelial cells were susceptible to SARS-CoV-2 infection[31] (Fig. 3b–d). Based on the RNA copies and the serological analyses of both inoculated and contact mice, we believed that B.1.351-infected mice could transmit the virus to uninfected mice via close contact
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