Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 13, 2024

Knockout of the ORF8 protein has repeatedly spread through global viral population during SARS-CoV-2 evolution. Here we use both regional and pathogen sequencing to explore selection pressures underlying its loss. In Washington State, identified transmission clusters with knockout throughout evolution, not just on novel, high fitness backbones. Indeed, is truncated more frequently knockouts circulate for longer than any other gene. Using a phylogeny, find evidence positive explain this phenomenon: nonsense mutations resulting in shortened products occur are associated faster clade growth rates synonymous ORF8. Loss also reduced clinical severity, highlighting diverse impacts

Язык: Английский

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Adaptive evolution of SARS-CoV-2 during a persistent infection for 521 days in an immunocompromised patient

npj Genomic Medicine, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 17, 2025

Immunocompromised patients struggle to adequately clear viral infections, offering the virus opportunity adapt immune system in host. Here we present a case study of patient undergoing allogeneic hematopoietic stem cell transplantation with 521-day follow-up SARS-CoV-2 infection BF.7.21 variant. Virus samples from five time points were submitted whole genome sequencing. Between first detection and its clearance, patient's population acquired 34 amino acid substitutions 8 deletions coding regions. With 11 receptor binding domain virus' spike protein, 15 times more abundant than expected for random distribution this highly functional region. Amongst them S:K417T, S:N440S, S:K444R, S:V445A, S:G446N, S:L452Q, S:N460K, S:E484V at positions that are notorious their resistance-mediating effects. The substitution patterns found indicate ongoing adaptive evolution.

Язык: Английский

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SARS-CoV-2 shedding and evolution in immunocompromised hosts during the Omicron period: a multicenter prospective analysis

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 24, 2023

ABSTRACT Background Prolonged SARS-CoV-2 infections in immunocompromised hosts may predict or source the emergence of highly mutated variants. The types immunosuppression placing patients at highest risk for prolonged infection and associated intrahost viral evolution remain unclear. Methods Adults aged ≥18 years were enrolled 5 hospitals followed from 4/11/2022 – 2/1/2023. Eligible SARS-CoV-2-positive previous 14 days had a moderate severely immunocompromising condition treatment. Nasal specimens tested by rRT-PCR every 2–4 weeks until negative consecutive specimens. Positive underwent culture whole genome sequencing. A Cox proportional hazards model was used to assess factors with duration infection. Results We 150 with: B cell malignancy anti-B therapy (n=18), solid organ hematopoietic stem transplant (SOT/HSCT) (n=59), AIDS (n=5), non-B (n=23), autoimmune/autoinflammatory conditions (n=45). Thirty-eight (25%) rRT-PCR-positive 12 (8%) culture-positive ≥21 after initial detection illness onset. Patients dysfunction longer rRT-PCR- positivity compared those (aHR 0.32, 95% CI 0.15-0.64). Consensus (>50% frequency) spike mutations identified individuals who >56 days; 61% receptor-binding domain (RBD). Mutations shared multiple rare (<5%) global circulation. Conclusions In this cohort, replication-competent Omicron uncommon. Within-host evolutionary rates similar across patients, but lasting accumulated mutations, which distinct seen globally.

Язык: Английский

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Machine Learning Early Detection of SARS‐CoV‐2 High‐Risk Variants

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Окт. 14, 2024

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has evolved many high‐risk variants, resulting in repeated COVID‐19 waves over the past years. Therefore, accurate early warning of variants is vital for epidemic prevention and control. However, detecting through experimental epidemiological research time‐consuming often lags behind emergence spread these variants. In this study, HiRisk‐Detector a machine learning algorithm based on haplotype network, developed computationally SARS‐CoV‐2 Leveraging 7.6 million high‐quality complete genomes metadata, effectiveness, robustness, generalizability are validated. First, evaluated actual empirical data, successfully all 13 preceding World Health Organization announcements by 27 days average. Second, its robustness tested reducing sequencing intensity to one‐fourth, noting only minimal delay 3.8 days, demonstrating effectiveness. Third, applied detect risks among Omicron variant sub‐lineages, confirming broad applicability high ROC‐AUC PR‐AUC performance. Overall, features powerful capacity detection bearing great utility any public emergency caused infectious diseases or viruses.

Язык: Английский

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VIPERA: Viral Intra-Patient Evolution Reporting and Analysis

Virus Evolution, Год журнала: 2024, Номер 10(1)

Опубликована: Янв. 1, 2024

Abstract Viral mutations within patients nurture the adaptive potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during chronic infections, which are a source variants concern. However, there is no integrated framework for evolutionary analysis intra-patient SARS-CoV-2 serial samples. Herein, we describe Intra-Patient Evolution Reporting and Analysis (VIPERA), new software that integrates evaluation ancestry sequences with trajectories from same viral infection. We have validated it using positive negative control datasets successfully applied to case, revealed population dynamics evidence evolution. VIPERA available under free license at https://github.com/PathoGenOmics-Lab/VIPERA.

Язык: Английский

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Case reports of persistent SARS-CoV-2 infection outline within-host viral evolution in immunocompromised patients

Virology Journal, Год журнала: 2024, Номер 21(1)

Опубликована: Сен. 3, 2024

Язык: Английский

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Persistent COVID-19 Infection in an Immunocompromised Host: A Case Report

Cureus, Год журнала: 2024, Номер unknown

Опубликована: Сен. 4, 2024

This case report highlights the prolonged SARS-CoV-2 reverse transcriptase polymerase chain reaction positivity in a 32-year-old immunocompromised male with history of kidney transplants and chronic disease. The whole genome sequencing nasopharyngeal samples for collected 12 days apart showed presence BA.1.1 Omicron variant. It revealed evidence intra-host viral evolution, showing development loss specific mutations over time. emphasizes need continuous monitoring strategies patients, as they may serve reservoirs evolution potentially give rise to immune escape variants.

Язык: Английский

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Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection

PLoS Pathogens, Год журнала: 2024, Номер 20(10), С. e1012624 - e1012624

Опубликована: Окт. 15, 2024

Neutralising antibodies against the SARS-CoV-2 spike (S) protein are major determinants of protective immunity, though insufficient antibody responses may cause emergence escape mutants. We studied humoral immune response causing intra-host evolution in a B-cell depleted, haemato-oncologic patient experiencing clinically severe, prolonged infection with virus lineage B.1.177.81. Following bamlanivimab treatment at an early stage infection, developed bamlanivimab-resistant mutation, S:S494P. After five weeks apparent genetic stability, additional substitutions and deletions within N-terminal domain (NTD) receptor binding (RBD) S was observed. Notably, composition frequency mutations changed short period unprecedented dynamic. The triple mutant S:Delta141-4 E484K S494P became dominant until elimination. Routine serology revealed no evidence patient. A detailed analysis variant-specific by pseudotyped neutralisation test, surrogate immunoglobulin-capture enzyme immunoassay showed that onset IgM-dominated coincided appearance mutations. formation neutralising correlated One year later, experienced mild re-infection Omicron BA.1.18, which treated sotrovimab resulted increase Omicron-reactive antibodies. In conclusion, endogenous immunocompromised NTD RBD virus. Although elimination ultimately achieved, this escaped detection routine diagnosis created situation temporarily favouring rapid various mutants known epidemiological relevance.

Язык: Английский

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The consequences of SARS-CoV-2 within-host persistence

Nature Reviews Microbiology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

Язык: Английский

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Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 4, 2024

Abstract Accumulating evidence points to persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals as a source of genetically divergent, novel lineages, generally characterised by increased transmissibility and immune escape. While intrahost evolutionary dynamics the virus chronically infected patients have been previously reported, existing knowledge is primarily based on samples obtained from nasopharyngeal compartment. In this study, we investigate evolution genetic diversity that accumulated during prolonged SARS-CoV-2 infection with Omicron sublineage BF.7, estimated persisted for over one year an immunosuppressed patient. Based sequencing eight viral genomes collected patient at six time points, identified 86 single-nucleotide variants (iSNVs), two indels, 362 bp deletion. Our analysis revealed distinct genotypes (NP), endotracheal aspirate (ETA), bronchoalveolar (BAL) samples. Notably, while significant divergence was observed between NP BAL samples, most iSNVs found ETA were also detected or This suggests may not offer comprehensive representation overall diversity. Nonsynonymous mutations frequent spike envelope genes, along loss-of-function ORF8, generated frameshift mutation large deletion respectively. Using long-range PCR sequenced part routine surveillance, validated similar deletions causing ORF8 loss function can be carried infection. findings only demonstrate BF.7 further diverge its already exceptionally mutated state but highlight develop specific populations across anatomical compartments. provides insights into intricate nature infections.

Язык: Английский

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