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Human airway and nasal organoids reveal escalating replicative fitness of SARS-CoV-2 emerging variants.
Li, Cun; Huang, Jingjing; Yu, Yifei; Wan, Zhixin; Chiu, Man Chun; Liu, Xiaojuan; Zhang, Shuxin; Cai, Jian-Piao; Chu, Hin; Li, Gang; Chan, Jasper Fuk-Woo; To, Kelvin Kai-Wang; Yang, Zifeng; Jiang, Shibo; Yuen, Kwok-Yung; Clevers, Hans; Zhou, Jie.
  • Li C; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Huang J; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Yu Y; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Wan Z; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Chiu MC; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Liu X; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Zhang S; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Cai JP; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Chu H; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Li G; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
  • Chan JF; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China.
  • To KK; Department of Otolaryngology-Head and Neck Surgery, Precision Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Yang Z; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Jiang S; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
  • Yuen KY; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China.
  • Clevers H; Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
  • Zhou J; Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Proc Natl Acad Sci U S A ; 120(17): e2300376120, 2023 04 25.
Article in English | MEDLINE | ID: covidwho-2298706
ABSTRACT
The high transmissibility of SARS-CoV-2 Omicron subvariants was generally ascribed to immune escape. It remained unclear whether the emerging variants have gradually acquired replicative fitness in human respiratory epithelial cells. We sought to evaluate the replicative fitness of BA.5 and earlier variants in physiologically active respiratory organoids. BA.5 exhibited a dramatically increased replicative capacity and infectivity than B.1.1.529 and an ancestral strain wildtype (WT) in human nasal and airway organoids. BA.5 spike pseudovirus showed a significantly higher entry efficiency than that carrying WT or B.1.1.529 spike. Notably, we observed prominent syncytium formation in BA.5-infected nasal and airway organoids, albeit elusive in WT- and B.1.1.529-infected organoids. BA.5 spike-triggered syncytium formation was verified by lentiviral overexpression of spike in nasal organoids. Moreover, BA.5 replicated modestly in alveolar organoids, with a significantly lower titer than B.1.1.529 and WT. Collectively, the higher entry efficiency and fusogenic activity of BA.5 spike potentiated viral spread through syncytium formation in the human airway epithelium, leading to enhanced replicative fitness and immune evasion, whereas the attenuated replicative capacity of BA.5 in the alveolar organoids may account for its benign clinical manifestation.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2023 Document Type: Article Affiliation country: Pnas.2300376120

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2023 Document Type: Article Affiliation country: Pnas.2300376120