tetano
Editor, Senior Moderator
Mol Cells
. 2022 Nov 2.
doi: 10.14348/molcells.2022.0089. Online ahead of print.
Temporal Transcriptome Analysis of SARS-CoV-2-Infected Lung and Spleen in Human ACE2-Transgenic Mice
Jung Ah Kim[SUP] 1 [/SUP], Sung-Hee Kim[SUP] 2 [/SUP], Jung Seon Seo[SUP] 2 [/SUP], Hyuna Noh[SUP] 3 [/SUP], Haengdueng Jeong[SUP] 2 [/SUP], Jiseon Kim[SUP] 2 [/SUP], Donghun Jeon[SUP] 2 [/SUP], Jeong Jin Kim[SUP] 2 [/SUP], Dain On[SUP] 3 4 [/SUP], Suhyeon Yoon[SUP] 3 [/SUP], Sang Gyu Lee[SUP] 5 [/SUP], Youn Woo Lee[SUP] 6 [/SUP], Hui Jeong Jang[SUP] 6 [/SUP], In Ho Park[SUP] 2 7 [/SUP], Jooyeon Oh[SUP] 8 [/SUP], Sang-Hyuk Seok[SUP] 9 [/SUP], Yu Jin Lee[SUP] 9 [/SUP], Seung-Min Hong[SUP] 10 [/SUP], Se-Hee An[SUP] 10 [/SUP], Joon-Yong Bae[SUP] 11 [/SUP], Jung-Ah Choi[SUP] 12 [/SUP], Seo Yeon Kim[SUP] 13 [/SUP], Young Been Kim[SUP] 13 [/SUP], Ji-Yeon Hwang[SUP] 13 [/SUP], Hyo-Jung Lee[SUP] 14 [/SUP], Hong Bin Kim[SUP] 15 [/SUP], Dae Gwin Jeong[SUP] 16 [/SUP], Daesub Song[SUP] 17 [/SUP], Manki Song[SUP] 12 [/SUP], Man-Seong Park[SUP] 11 [/SUP], Kang-Seuk Choi[SUP] 10 [/SUP], Jun Won Park[SUP] 9 [/SUP], Jun-Won Yun[SUP] 18 [/SUP], Jeon-Soo Shin[SUP] 2 7 8 [/SUP], Ho-Young Lee[SUP] 6 19 [/SUP], Jun-Young Seo[SUP] 2 [/SUP], Ki Taek Nam[SUP] 2 [/SUP], Heon Yung Gee[SUP] 1 [/SUP], Je Kyung Seong[SUP] 3 4 5 20 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.
Keywords: SARS-CoV-2; immune-mediated response; transcriptome profiling.
. 2022 Nov 2.
doi: 10.14348/molcells.2022.0089. Online ahead of print.
Temporal Transcriptome Analysis of SARS-CoV-2-Infected Lung and Spleen in Human ACE2-Transgenic Mice
Jung Ah Kim[SUP] 1 [/SUP], Sung-Hee Kim[SUP] 2 [/SUP], Jung Seon Seo[SUP] 2 [/SUP], Hyuna Noh[SUP] 3 [/SUP], Haengdueng Jeong[SUP] 2 [/SUP], Jiseon Kim[SUP] 2 [/SUP], Donghun Jeon[SUP] 2 [/SUP], Jeong Jin Kim[SUP] 2 [/SUP], Dain On[SUP] 3 4 [/SUP], Suhyeon Yoon[SUP] 3 [/SUP], Sang Gyu Lee[SUP] 5 [/SUP], Youn Woo Lee[SUP] 6 [/SUP], Hui Jeong Jang[SUP] 6 [/SUP], In Ho Park[SUP] 2 7 [/SUP], Jooyeon Oh[SUP] 8 [/SUP], Sang-Hyuk Seok[SUP] 9 [/SUP], Yu Jin Lee[SUP] 9 [/SUP], Seung-Min Hong[SUP] 10 [/SUP], Se-Hee An[SUP] 10 [/SUP], Joon-Yong Bae[SUP] 11 [/SUP], Jung-Ah Choi[SUP] 12 [/SUP], Seo Yeon Kim[SUP] 13 [/SUP], Young Been Kim[SUP] 13 [/SUP], Ji-Yeon Hwang[SUP] 13 [/SUP], Hyo-Jung Lee[SUP] 14 [/SUP], Hong Bin Kim[SUP] 15 [/SUP], Dae Gwin Jeong[SUP] 16 [/SUP], Daesub Song[SUP] 17 [/SUP], Manki Song[SUP] 12 [/SUP], Man-Seong Park[SUP] 11 [/SUP], Kang-Seuk Choi[SUP] 10 [/SUP], Jun Won Park[SUP] 9 [/SUP], Jun-Won Yun[SUP] 18 [/SUP], Jeon-Soo Shin[SUP] 2 7 8 [/SUP], Ho-Young Lee[SUP] 6 19 [/SUP], Jun-Young Seo[SUP] 2 [/SUP], Ki Taek Nam[SUP] 2 [/SUP], Heon Yung Gee[SUP] 1 [/SUP], Je Kyung Seong[SUP] 3 4 5 20 [/SUP]
Affiliations
- PMID: 36324270
- DOI: 10.14348/molcells.2022.0089
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.
Keywords: SARS-CoV-2; immune-mediated response; transcriptome profiling.