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bioRxiv · 10.1101/2022.02.07.479352

A highly attenuated SARS-CoV-2 related pangolin coronavirus variant has a 104nt deletion at the 3'-terminus untranslated region

Lu, S.·Luo, S.·Liu, C.·Li, M.·An, X.·Hou, J.·Fan, H.·Mao, P.·Tong, Y.-G.·Song, L.
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Abstract

SARS-CoV-2 related coronaviruses (SARS-CoV-2r) from Guangdong and Guangxi pangolins have been implicated in the emergence of SARS-CoV-2 and future pandemics. We previously reported the culture of a SARS-CoV-2r GX_P2V from Guangxi pangolins. Here we report the GX_P2V isolate rapidly adapted to Vero cells by acquiring two genomic mutations: an alanine to valine substitution in the nucleoprotein and a 104-nucleotide deletion in the hypervariable region (HVR) of the 3-terminus untranslated region (3-UTR). We further report the characterization of the GX_P2V variant in in vitro and in vivo infection models. In cultured Vero and BGM cells, the GX_P2V variant produced minimal cell damage and small plaques. The GX_P2V variant infected golden hamsters and BALB/c mice but was highly attenuated. Golden hamsters infected intranasally had a short duration of productive infection. These productive infections induced neutralizing antibodies against pseudoviruses of GX_P2V and SARS-CoV-2. Collectively, our data show that the GX_P2V variant is highly attenuated in in vitro and in vivo infection models. Attenuation of the variant is likely due to the 104-nt deletion in the HVR in the 3-UTR. This study furthers our understanding of pangolin coronaviruses pathogenesis and provides novel insights for the design of live attenuated vaccines against SARS-CoV-2.

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Lu, S., Luo, S., Liu, C., Li, M., An, X., Hou, J., Fan, H., Mao, P., Tong, Y.-G., Song, L.. 2022-02-08. A highly attenuated SARS-CoV-2 related pangolin coronavirus variant has a 104nt deletion at the 3'-terminus untranslated region. https://doi.org/10.1101/2022.02.07.479352

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