tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2022 Dec 1;1-47.
doi: 10.1080/22221751.2022.2151383. Online ahead of print.
Induction of Significant Neutralizing Antibodies against SARS-CoV-2 by a Highly Attenuated Pangolin Coronavirus Variant with a 104nt Deletion at the 3'-UTR
Shanshan Lu[SUP] 1 [/SUP], Shengdong Luo[SUP] 2 [/SUP], Chang Liu[SUP] 1 [/SUP], Muli Li[SUP] 3 [/SUP], Xiaoping An[SUP] 1 [/SUP], Mengzhe Li[SUP] 1 [/SUP], Jun Hou[SUP] 2 [/SUP], Huahao Fan[SUP] 1 [/SUP], Panyong Mao[SUP] 2 [/SUP], Yigang Tong[SUP] 1 [/SUP], Lihua Song[SUP] 1 [/SUP]
Affiliations
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 (renamed GX_P2V(short_3UTR)) in in vitro and in vivo infection models. In cultured Vero, BGM and Calu-3 cells, GX_P2V(short_3UTR) had similar robust replication kinetics, and consistently produced minimum cell damage. GX_P2V(short_3UTR) infected golden hamsters and BALB/c mice but was highly attenuated. Golden hamsters infected intranasally had a short duration of productive infection in pulmonary, not extrapulmonary, tissues. These productive infections induced neutralizing antibodies against pseudoviruses of GX_P2V and SARS-CoV-2. Collectively, our data show that the GX_P2V(short_3UTR) is highly attenuated in in vitro and in vivo infection models. Attenuation of the variant is likely partially 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.
Keywords: Coronavirus; Pangolin coronavirus; SARS-CoV-2; live attenuated vaccine; neutralizing antibody.
. 2022 Dec 1;1-47.
doi: 10.1080/22221751.2022.2151383. Online ahead of print.
Induction of Significant Neutralizing Antibodies against SARS-CoV-2 by a Highly Attenuated Pangolin Coronavirus Variant with a 104nt Deletion at the 3'-UTR
Shanshan Lu[SUP] 1 [/SUP], Shengdong Luo[SUP] 2 [/SUP], Chang Liu[SUP] 1 [/SUP], Muli Li[SUP] 3 [/SUP], Xiaoping An[SUP] 1 [/SUP], Mengzhe Li[SUP] 1 [/SUP], Jun Hou[SUP] 2 [/SUP], Huahao Fan[SUP] 1 [/SUP], Panyong Mao[SUP] 2 [/SUP], Yigang Tong[SUP] 1 [/SUP], Lihua Song[SUP] 1 [/SUP]
Affiliations
- PMID: 36453209
- DOI: 10.1080/22221751.2022.2151383
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 (renamed GX_P2V(short_3UTR)) in in vitro and in vivo infection models. In cultured Vero, BGM and Calu-3 cells, GX_P2V(short_3UTR) had similar robust replication kinetics, and consistently produced minimum cell damage. GX_P2V(short_3UTR) infected golden hamsters and BALB/c mice but was highly attenuated. Golden hamsters infected intranasally had a short duration of productive infection in pulmonary, not extrapulmonary, tissues. These productive infections induced neutralizing antibodies against pseudoviruses of GX_P2V and SARS-CoV-2. Collectively, our data show that the GX_P2V(short_3UTR) is highly attenuated in in vitro and in vivo infection models. Attenuation of the variant is likely partially 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.
Keywords: Coronavirus; Pangolin coronavirus; SARS-CoV-2; live attenuated vaccine; neutralizing antibody.