Quasispecies theory and emerging viruses: challenges and applications

npj Viruses, Journal Year: 2024, Volume and Issue: 2(1)

Published: Nov. 14, 2024

Quasispecies theory revolutionized our understanding of viral evolution by describing viruses as dynamic populations genetically diverse variants constantly adapting. This article explores the theory's role in virus-host interactions, including immune evasion, drug resistance, and emergence. We review original model, recent advances, key virus dynamics needing incorporation into quasispecies theory. introduce ultracube concept a more realistic multidimensional sequence space to investigate evolutionary dynamics.

Language: Английский

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Analysis of NS2-dependent effects on influenza PB1 segment extends replication requirements beyond the canonical promoter

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 22, 2025

Abstract Influenza A virus encodes conserved promoter sequences. Using minimal replication assays—transfections with viral polymerase, nucleoprotein, and a genomic template—these sequences were identified as 13nt at the 5’ end of RNA (U13) 12nt 3’ (U12). Other than fourth nucleotide, U12 U13 are identical between all eight molecules segmented influenza genome. However, individual segments can exhibit different dynamics during infection. NS2, which modulates transcription differentially segments, may provide an explanation. Here, we assess how internal two HA PB1, contribute to NS2-dependent map such interactions down nucleotides in PB1. We find that expression NS2 significantly alters sequence requirements for efficient beyond sequences, providing potential mechanism segment-specific across

Language: Английский

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Exploiting social traits for clinical applications in bacteria and viruses

npj Antimicrobials and Resistance, Journal Year: 2025, Volume and Issue: 3(1)

Published: March 28, 2025

Despite generating a great deal of interest in the form review papers, progress exploiting social dynamics for treatment strategies against bacterial infection has made limited since it was suggested twenty years ago. In contrast, anti-viral based on interactions are entering clinical trial stage. We explore possible reasons this difference and highlight areas where two fields research may learn from one another.

Language: Английский

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Deletion detection in SARS-CoV-2 genomes using multiplex-PCR sequencing from COVID-19 patients: elimination of false positives

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Deletions are prevalent in the genomes of SARS-CoV-2 isolates from COVID-19 patients, but their roles severity, transmission, and persistence disease poorly understood. Millions swab samples patients have been sequenced made available online, offering an unprecedented opportunity to study such deletions. Multiplex PCR-based amplicon sequencing (amplicon-seq) has most widely used method for clinical samples. However, existing bioinformatics methods applied negative control by multiplex-PCR often yield large numbers false-positive We found that these false positives commonly occur short alignments, at low frequency depth, near primer-binding sites whole-genome amplification. To address this issue, we developed a filtering strategy, validated with positive containing known deletion. Our strategy accurately detected deletion removed more than 99% positives. This method, public data, revealed deletions occurring independently transcription regulatory sequences were about 20-fold less common previously reported; however, they remain frequent symptomatic patients. optimized approach should enhance reliability characterization surveillance studies. Finally, our may guide development reliable pipelines genome sequence analyses other viruses.

Language: Английский

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Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 12, 2023

Productive infections by RNA viruses require faithful replication of the entire genome. Yet many also produce deletion-containing viral genomes (DelVGs), aberrant products with large internal deletions. DelVGs interfere wild-type virus and their presence in patients is associated better clinical outcomes as they. The DelVG itself hypothesized to confer this interfering activity. antagonize out-competing full-length genome triggering innate immune responses. Here, we identify an additionally inhibitory mechanism mediated a new class proteins encoded DelVGs. We identified hundreds cryptic translated from These DelVG-encoded (DPRs) include canonical deletions, well novel C-termini alternative reading frames. Many DPRs retain functional domains shared counterparts, suggesting they may have activity during infection. Mechanistic studies derived influenza protein PB2 showed that poison acting dominant-negative inhibitors polymerase. findings reveal dual mechanism, at both level. They further show potential dramatically expand proteomes diverse viruses.

Language: Английский

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Efficient genome replication in influenza A virus requires NS2 and sequence beyond the canonical promoter

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Influenza A virus encodes promoters in both the sense and antisense orientations. These support generation of new genomes, antigenomes, mRNA transcripts. Using minimal replication assays-transfections with viral polymerase, nucleoprotein, a genomic template-the influenza promoter sequences were identified as 13nt at 5' end RNA (U13) 12nt 3' (U12). Other than fourth nucleotide, U12 U13 are identical between all eight molecules that comprise segmented genome. Despite possessing promoters, individual segments can exhibit different transcriptional dynamics during infection. However flu defined experiments without NS2, protein which modulates transcription differentially segments. This suggests identity "complete" may depend on NS2. Here we assess how internal two segments, HA PB1, contribute to NS2-dependent well map such interactions down nucleotides PB1. We find expression NS2 significantly alters sequence requirements for efficient beyond sequence, providing mechanism divergent across

Language: Английский

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