Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2

Kistler, Kathryn E.; Huddleston, John; Bedford, Trevor

doi:10.1016/j.chom.2022.03.018

Cited by 80 publications

(73 citation statements)

References 49 publications

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“…This enrichment is primarily driven by S:P681H/R, a highly recurrent globally occurring mutation 29 , surprisingly never observed in our chronic infection set. A recent study analyzed recurrent mutations, with recurrence indicative of positive selection, and tested which of the recurrent mutations led to clade expansion—that is, were associated with onwards transmission 30 . Some recurrent mutations led to more dense clades, suggesting that they were especially successful in driving transmission, whereas others did not lead to considerable onwards transmission, suggesting that they were less successful.…”

Section: Resultsmentioning

confidence: 99%

“… High clade success or low clade success is reported based on measurements of clade logistic growth, with + or – representing higher or lower than average growth, respectively 30 . The last column marks the number of patients in the set of chronic infections herein where a substitution was observed.…”

Section: Resultsmentioning

confidence: 99%

“…However, globally circulating variants bearing these mutations were inferred to be less transmissible than variants bearing other highly recurrent mutations (Table 2 and ref. 30 ). On the other hand, several mutations associated with higher transmissibility (for example, S:P681R and ORF1a:∆3,675–3,677) 30 were never observed in the chronic infections herein (Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

“… 30 ). On the other hand, several mutations associated with higher transmissibility (for example, S:P681R and ORF1a:∆3,675–3,677) 30 were never observed in the chronic infections herein (Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

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Drivers of adaptive evolution during chronic SARS-CoV-2 infections

Harari

Tahor

Rutsinsky

et al. 2022

Nat Med

101

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In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient’s body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Drivers of adaptive evolution during chronic SARS-CoV-2 infections

Harari

Tahor

Rutsinsky

et al. 2022

Nat Med

101

View full text Add to dashboard Cite

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“…NSP6 decreases the autophagic capacity of infected cells, which provides an innate defense against viral infections ( Mercatelli and Giorgi, 2020 ). Most recently, the accumulation of mutations in S1 subunit of S protein was found to be associated with ORF1a: 3,675–3,677 deletion and this deletion was indicated as an adaptive mutation that facilitates the process of SARS-CoV-2 evolution ( Kistler et al, 2022 ). One coding mutation was found in N protein.…”

Section: Discussionmentioning

confidence: 99%

A Mouse-Adapted Model of HCoV-OC43 and Its Usage to the Evaluation of Antiviral Drugs

et al. 2022

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The human coronavirus OC43 (HCoV-OC43) is one of the most common causes of common cold but can lead to fatal pneumonia in children and elderly. However, the available animal models of HCoV-OC43 did not show respiratory symptoms that are insufficient to assist in screening antiviral agents for respiratory diseases. In this study, we adapted the HCoV-OC43 VR-1558 strain by serial passage in suckling C57BL/6 mice and the resulting mouse-adapted virus at passage 9 (P9) contained 8 coding mutations in polyprotein 1ab, spike (S) protein, and nucleocapsid (N) protein. Pups infected with the P9 virus significantly lost body weight and died within 5 dpi. In cerebral and pulmonary tissues, the P9 virus replication induced the production of G-CSF, IFN-γ, IL-6, CXCL1, MCP-1, MIP-1α, RANTES, IP-10, MIP-1β, and TNF-α, as well as pathological alterations including reduction of neuronal cells and typical symptoms of viral pneumonia. We found that the treatment of arbidol hydrochloride (ARB) or Qingwenjiere Mixture (QJM) efficiently improved the symptoms and decreased n gene expression, inflammatory response, and pathological changes. Furthermore, treating with QJM or ARB raised the P9-infected mice’s survival rate within a 15 day observation period. These findings suggested that the new mouse-adapted HCoV-OC43 model is applicable and reproducible for antiviral studies of HCoV-OC43.

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