Abstract
SARS-CoV-2 variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) variants, have displayed increased transmissibility and, therefore, have been categorized as variants of concern (VOCs). The pervasiveness of VOCs suggests a high probability of future mutations that may lead to increased virulence. Prior reports have shown that VOC infection without expression of human angiotensin converting enzyme-2 receptor (hACE2) in mice is possible. We sought to understand if the increased transmissibility of VOCs can infect C57BL/6 mice without expression of hACE2 receptor required for entry of SARS-CoV-2 normally. We examined the ability of infection with Beta and Gamma variants to infect and cause both pathological and clinical changes consistent with severe COVID-19, including body weight changes, survival, subgenomic viral titer, lung histology on Hematoxylin and Eosin (H&E) staining, and viral protein expression as measured by immunohistochemistry staining of viral antigen (IHC). These methods were used to examine three groups of mice: C57BL6, Rag2 -/-, and Ccr2 -/- mice. We observed that these mice, infected with Beta and Gamma variants of SARS-CoV-2, did not show pathological changes as indicated by weight loss, altered survival, or significant lung pathology on H&E staining. Subgenomic qPCR and IHC staining for viral protein indicated that there was some evidence of infection but far below ACE2 transgenic mice, which showed clinical disease and pathologic changes consistent with ARDS. These data suggest that these variants replicate poorly even in the setting of profound immune deficiency.
Keywords: SARS-CoV-2; immunocompromised mice; variants of concern.
【저자키워드】 SARS-CoV-2, variants of concern., immunocompromised mice, 【초록키워드】 immunohistochemistry, ACE2, ARDS, Mutation, severe COVID-19, VoC, B.1.351, body weight, variant, Infection, variants of concern, Delta, B.1.617.2, lung, variants, immune, hACE2, Angiotensin converting enzyme-2, Probability, survival, Transmissibility, SARS-CoV-2 variants, B.1.1.7, mice, qPCR, P.1, VOCs, Immunocompromised, Gamma, Alpha, Beta, receptor, virulence, histology, expression, change, Lung pathology, Evidence, angiotensin, evidence of, immune deficiency, Body Weight Changes, changes, weight loss, deficiency, Viral antigen, CCR2, Viral protein, eosin, hematoxylin, These data, transgenic mice, three groups, hACE2 receptor, staining, clinical disease, pathological changes, viral titer, variants of SARS-CoV-2, infect, C57BL/6, IHC, IHC staining, RAG2, shown, examined, pathologic, indicated, required, replicate, were used, pathological change, three group, entry of SARS-CoV-2, H&E, H&E staining, 【제목키워드】 modeling, Gamma,