Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids

Autor: Min Jung Kim, Sumi Kim, Heeyeon Kim, Dayeon Gil, Hyeong-Jun Han, Rajesh K. Thimmulappa, Jang-Hoon Choi, Jung-Hyun Kim
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Emerging Microbes and Infections, Vol 12, Iss 1 (2023)
Druh dokumentu: article
ISSN: 22221751
2222-1751
DOI: 10.1080/22221751.2023.2211685
Popis: ABSTRACTPatients 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. 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. A single virus markedly enhanced the susceptibility to other virus infections. 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). Moreover, 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. This study 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 therapeutics for such co-infection cases.
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