한빛사논문
- 조회418
Min Jung Kim 1,2, Sumi Kim 3, Heeyeon Kim 3, Dayeon Gil 1,2, Hyeong-Jun Han 1,2, Rajesh K Thimmulappa 4, Jang-Hoon Choi 3, Jung-Hyun Kim 1,2
1Division of Intractable Diseases Research, Department of Chronic Diseases Convergence Research, Korea National Institute of Health, Cheongju, Korea.
2Korea National Stem Cell Bank, Cheongju, South Korea.
3Division of Acute Viral Disease, Center for Emerging Virus Research, National Institute of Infectious Diseases, Korea National Institute of Health, Cheongju, Korea.
4Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru 570015, India.
Correspondence : Jang-Hoon Choi, Jung-Hyun Kim
Abstract
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.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-05-30)
- 국내(교신)+국외 연구진
- 생명과학 > 미생물학
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