tetano
Editor, Senior Moderator
Cell Rep
. 2024 Apr 10;43(4):114076.
doi: 10.1016/j.celrep.2024.114076. Online ahead of print. SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia
Rita M Meganck[SUP] 1 [/SUP], Caitlin E Edwards[SUP] 1 [/SUP], Michael L Mallory[SUP] 1 [/SUP], Rhianna E Lee[SUP] 2 [/SUP], Hong Dang[SUP] 2 [/SUP], Alexis B Bailey[SUP] 1 [/SUP], Jason A Wykoff[SUP] 2 [/SUP], Samuel C Gallant[SUP] 2 [/SUP], Deanna R Zhu[SUP] 1 [/SUP], Boyd L Yount[SUP] 1 [/SUP], Takafumi Kato[SUP] 2 [/SUP], Kendall M Shaffer[SUP] 2 [/SUP], Satoko Nakano[SUP] 2 [/SUP], Anne Marie Cawley[SUP] 2 [/SUP], Vishwaraj Sontake[SUP] 3 [/SUP], Jeremy R Wang[SUP] 4 [/SUP], Robert S Hagan[SUP] 5 [/SUP], Melissa B Miller[SUP] 6 [/SUP], Purushothama Rao Tata[SUP] 3 [/SUP], Scott H Randell[SUP] 2 [/SUP], Longping V Tse[SUP] 7 [/SUP], Camille Ehre[SUP] 2 [/SUP], Kenichi Okuda[SUP] 2 [/SUP], Richard C Boucher[SUP] 2 [/SUP], Ralph S Baric[SUP] 8 [/SUP]
Affiliations
The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3' end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence.
Keywords: CP: Microbiology; SARS-CoV-2; adaptation; cellular tropism; competition; coronavirus; primary airway culture; recombination; single cell RNA-seq; variants of concern; viral fitness.
. 2024 Apr 10;43(4):114076.
doi: 10.1016/j.celrep.2024.114076. Online ahead of print. SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia
Rita M Meganck[SUP] 1 [/SUP], Caitlin E Edwards[SUP] 1 [/SUP], Michael L Mallory[SUP] 1 [/SUP], Rhianna E Lee[SUP] 2 [/SUP], Hong Dang[SUP] 2 [/SUP], Alexis B Bailey[SUP] 1 [/SUP], Jason A Wykoff[SUP] 2 [/SUP], Samuel C Gallant[SUP] 2 [/SUP], Deanna R Zhu[SUP] 1 [/SUP], Boyd L Yount[SUP] 1 [/SUP], Takafumi Kato[SUP] 2 [/SUP], Kendall M Shaffer[SUP] 2 [/SUP], Satoko Nakano[SUP] 2 [/SUP], Anne Marie Cawley[SUP] 2 [/SUP], Vishwaraj Sontake[SUP] 3 [/SUP], Jeremy R Wang[SUP] 4 [/SUP], Robert S Hagan[SUP] 5 [/SUP], Melissa B Miller[SUP] 6 [/SUP], Purushothama Rao Tata[SUP] 3 [/SUP], Scott H Randell[SUP] 2 [/SUP], Longping V Tse[SUP] 7 [/SUP], Camille Ehre[SUP] 2 [/SUP], Kenichi Okuda[SUP] 2 [/SUP], Richard C Boucher[SUP] 2 [/SUP], Ralph S Baric[SUP] 8 [/SUP]
Affiliations
- PMID: 38607917
- DOI: 10.1016/j.celrep.2024.114076
The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3' end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence.
Keywords: CP: Microbiology; SARS-CoV-2; adaptation; cellular tropism; competition; coronavirus; primary airway culture; recombination; single cell RNA-seq; variants of concern; viral fitness.