tetano
Editor, Senior Moderator
Immune Netw
. 2024 Feb 2;24(2):e7.
doi: 10.4110/in.2024.24.e7. eCollection 2024 Apr. Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice
Jung Ah Kim[SUP] 1 [/SUP], Sung-Hee Kim[SUP] 2 [/SUP], Jeong Jin Kim[SUP] 2 [/SUP], Hyuna Noh[SUP] 3 [/SUP], Su-Bin Lee[SUP] 4 [/SUP], Haengdueng Jeong[SUP] 2 [/SUP], Jiseon Kim[SUP] 2 [/SUP], Donghun Jeon[SUP] 2 [/SUP], Jung Seon Seo[SUP] 2 [/SUP], Dain On[SUP] 3 5 [/SUP], Suhyeon Yoon[SUP] 3 [/SUP], Sang Gyu Lee[SUP] 6 [/SUP], Youn Woo Lee[SUP] 7 [/SUP], Hui Jeong Jang[SUP] 7 [/SUP], In Ho Park[SUP] 2 8 [/SUP], Jooyeon Oh[SUP] 9 [/SUP], Sang-Hyuk Seok[SUP] 10 [/SUP], Yu Jin Lee[SUP] 10 [/SUP], Seung-Min Hong[SUP] 11 [/SUP], Se-Hee An[SUP] 11 [/SUP], Joon-Yong Bae[SUP] 12 [/SUP], Jung-Ah Choi[SUP] 13 [/SUP], Seo Yeon Kim[SUP] 14 [/SUP], Young Been Kim[SUP] 14 [/SUP], Ji-Yeon Hwang[SUP] 14 [/SUP], Hyo-Jung Lee[SUP] 15 [/SUP], Hong Bin Kim[SUP] 16 [/SUP], Dae Gwin Jeong[SUP] 17 [/SUP], Daesub Song[SUP] 18 [/SUP], Manki Song[SUP] 13 [/SUP], Man-Seong Park[SUP] 12 [/SUP], Kang-Seuk Choi[SUP] 11 [/SUP], Jun Won Park[SUP] 10 [/SUP], Jun-Won Yun[SUP] 19 [/SUP], Jeon-Soo Shin[SUP] 2 8 9 [/SUP], Ho-Young Lee[SUP] 7 20 [/SUP], Ho-Keun Kwon[SUP] 4 [/SUP], Jun-Young Seo[SUP] 2 [/SUP], Ki Taek Nam[SUP] 2 [/SUP], Heon Yung Gee[SUP] 1 [/SUP], Je Kyung Seong[SUP] 3 5 6 21 [/SUP]
Affiliations
Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10[SUP]5[/SUP] plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10[SUP]2[/SUP] PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10[SUP]2[/SUP] PFU-virus-infected lungs from 2 dpi, but not in 1×10[SUP]5[/SUP] PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10[SUP]5[/SUP] PFU; however, 1×10[SUP]2[/SUP] PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
Keywords: Dose-response relationship, immunologic; Immune response; K18-hACE2 mice; SARS-CoV-2; Transcriptome profiling.
. 2024 Feb 2;24(2):e7.
doi: 10.4110/in.2024.24.e7. eCollection 2024 Apr. Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice
Jung Ah Kim[SUP] 1 [/SUP], Sung-Hee Kim[SUP] 2 [/SUP], Jeong Jin Kim[SUP] 2 [/SUP], Hyuna Noh[SUP] 3 [/SUP], Su-Bin Lee[SUP] 4 [/SUP], Haengdueng Jeong[SUP] 2 [/SUP], Jiseon Kim[SUP] 2 [/SUP], Donghun Jeon[SUP] 2 [/SUP], Jung Seon Seo[SUP] 2 [/SUP], Dain On[SUP] 3 5 [/SUP], Suhyeon Yoon[SUP] 3 [/SUP], Sang Gyu Lee[SUP] 6 [/SUP], Youn Woo Lee[SUP] 7 [/SUP], Hui Jeong Jang[SUP] 7 [/SUP], In Ho Park[SUP] 2 8 [/SUP], Jooyeon Oh[SUP] 9 [/SUP], Sang-Hyuk Seok[SUP] 10 [/SUP], Yu Jin Lee[SUP] 10 [/SUP], Seung-Min Hong[SUP] 11 [/SUP], Se-Hee An[SUP] 11 [/SUP], Joon-Yong Bae[SUP] 12 [/SUP], Jung-Ah Choi[SUP] 13 [/SUP], Seo Yeon Kim[SUP] 14 [/SUP], Young Been Kim[SUP] 14 [/SUP], Ji-Yeon Hwang[SUP] 14 [/SUP], Hyo-Jung Lee[SUP] 15 [/SUP], Hong Bin Kim[SUP] 16 [/SUP], Dae Gwin Jeong[SUP] 17 [/SUP], Daesub Song[SUP] 18 [/SUP], Manki Song[SUP] 13 [/SUP], Man-Seong Park[SUP] 12 [/SUP], Kang-Seuk Choi[SUP] 11 [/SUP], Jun Won Park[SUP] 10 [/SUP], Jun-Won Yun[SUP] 19 [/SUP], Jeon-Soo Shin[SUP] 2 8 9 [/SUP], Ho-Young Lee[SUP] 7 20 [/SUP], Ho-Keun Kwon[SUP] 4 [/SUP], Jun-Young Seo[SUP] 2 [/SUP], Ki Taek Nam[SUP] 2 [/SUP], Heon Yung Gee[SUP] 1 [/SUP], Je Kyung Seong[SUP] 3 5 6 21 [/SUP]
Affiliations
- PMID: 38725670
- PMCID: PMC11076298
- DOI: 10.4110/in.2024.24.e7
Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10[SUP]5[/SUP] plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10[SUP]2[/SUP] PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10[SUP]2[/SUP] PFU-virus-infected lungs from 2 dpi, but not in 1×10[SUP]5[/SUP] PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10[SUP]5[/SUP] PFU; however, 1×10[SUP]2[/SUP] PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
Keywords: Dose-response relationship, immunologic; Immune response; K18-hACE2 mice; SARS-CoV-2; Transcriptome profiling.