tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2023 May 10;2211685.
doi: 10.1080/22221751.2023.2211685. Online ahead of print. Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids
Min Jung Kim[SUP] 1 2 [/SUP], Sumi Kim[SUP] 3 [/SUP], Heeyeon Kim[SUP] 3 [/SUP], Dayeon Gil[SUP] 1 2 [/SUP], Hyeong-Jun Han[SUP] 1 2 [/SUP], Rajesh K Thimmulappa[SUP] 4 [/SUP], Jang-Hoon Choi[SUP] 3 [/SUP], Jung-Hyun Kim[SUP] 1 2 [/SUP]
Affiliations
Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Because of the lack of a relevant lung model system, the pathobiology of co-infections between SARS-CoV-2 and FLUAV remains less understood. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage. We found that infection with a single virus markedly enhanced the susceptibility to other virus infections and was linked with the upregulation of respective cell entry receptors. SARS-CoV-2 delta variants upregulated α-2-3-linked sialic acid, while FLUAV upregulated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Upregulation of ACE2 and TMPRSS2 was mediated by the FLUAV infection rather than individual viral proteins. RNA sequencing revealed that coinfection by SARS-CoV-2 and FLUAV caused hyperactivation of proinflammatory and immune-related signaling pathways and cellular damage compared to a respective single virus in hiAT2 organoids. Together, these studies established a relevant lung model system of hiAT2 organoids for understanding the biology of SARS-CoV-2 and FLUAV coinfection. This study also provides insight into molecular mechanisms underlying enhanced infectivity and severity in patients with co-infection of SARS-CoV-2 and FLUAV, which may aid in the development of newer therapeutics for the prevention and management of such co-infection cases.
Keywords: Delta variant; Influenza A virus; Omicron variant; SARS-CoV-2; viral entry receptor; word.
. 2023 May 10;2211685.
doi: 10.1080/22221751.2023.2211685. Online ahead of print. Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids
Min Jung Kim[SUP] 1 2 [/SUP], Sumi Kim[SUP] 3 [/SUP], Heeyeon Kim[SUP] 3 [/SUP], Dayeon Gil[SUP] 1 2 [/SUP], Hyeong-Jun Han[SUP] 1 2 [/SUP], Rajesh K Thimmulappa[SUP] 4 [/SUP], Jang-Hoon Choi[SUP] 3 [/SUP], Jung-Hyun Kim[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37161660
- DOI: 10.1080/22221751.2023.2211685
Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Because of the lack of a relevant lung model system, the pathobiology of co-infections between SARS-CoV-2 and FLUAV remains less understood. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage. We found that infection with a single virus markedly enhanced the susceptibility to other virus infections and was linked with the upregulation of respective cell entry receptors. SARS-CoV-2 delta variants upregulated α-2-3-linked sialic acid, while FLUAV upregulated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Upregulation of ACE2 and TMPRSS2 was mediated by the FLUAV infection rather than individual viral proteins. RNA sequencing revealed that coinfection by SARS-CoV-2 and FLUAV caused hyperactivation of proinflammatory and immune-related signaling pathways and cellular damage compared to a respective single virus in hiAT2 organoids. Together, these studies established a relevant lung model system of hiAT2 organoids for understanding the biology of SARS-CoV-2 and FLUAV coinfection. This study also provides insight into molecular mechanisms underlying enhanced infectivity and severity in patients with co-infection of SARS-CoV-2 and FLUAV, which may aid in the development of newer therapeutics for the prevention and management of such co-infection cases.
Keywords: Delta variant; Influenza A virus; Omicron variant; SARS-CoV-2; viral entry receptor; word.