SARS-CoV-2 Variants, Vaccines, and Host Immunity

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 3, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new beta that emerged at the end of 2019 in Hubei province China. SARS-CoV-2 causes disease (COVID-19) and was declared pandemic by World Health Organization (WHO) on 11 March 2020. Herd or community immunity has been proposed as strategy to protect vulnerable, can be established through from past infection vaccination. Whether results development reservoir resilient memory cells under investigation. Vaccines have developed an unprecedented rate 7 408 870 760 vaccine doses administered worldwide. Recently variants are more transmissible with reduced sensitivity immune mechanisms. This due presence amino acid substitutions spike protein, which confer selective advantage. The emergence therefore poses risk for effectiveness long-term immunity, it crucial determine vaccines against currently circulating variants. Here we review both SARS-CoV-2-induced host activation vaccine-induced responses, highlighting responses key indicators immunity. We further discuss how emerge concern (VOC), particular focus implications effectiveness. Finally, describe antibody treatments future approaches will important navigate COVID-19 pandemic.

Language: Английский

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Omicron: What Makes the Latest SARS-CoV-2 Variant of Concern So Concerning?

Journal of Virology, Journal Year: 2022, Volume and Issue: 96(6)

Published: Feb. 28, 2022

Emerging strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent disease 2019 (COVID-19) pandemic, that show increased transmission fitness and/or immune evasion are classified as "variants concern" (VOCs). Recently, a SARS-CoV-2 variant first identified in November 2021 South Africa has been recognized fifth VOC, termed "Omicron." What makes this VOC so alarming is high number changes, especially viral Spike protein, and accumulating evidence for efficiency escape from neutralizing antibodies. In an amazingly short time, Omicron outcompeted previously dominating Delta VOC. However, it seems overall less pathogenic than other VOCs. Here, we provide overview mutations genome resulting changes proteins compared to discuss their potential functional consequences.

Language: Английский

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Divergent SARS-CoV-2 variant emerges in white-tailed deer with deer-to-human transmission

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(12), P. 2011 - 2024

Published: Nov. 10, 2022

Wildlife reservoirs of broad-host-range viruses have the potential to enable evolution viral variants that can emerge infect humans. In North America, there is phylogenomic evidence continual transmission severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans white-tailed deer (Odocoileus virginianus) through unknown means, but no We carried out an observational surveillance study in Ontario, Canada during November and December 2021 (n = 300 deer) identified a highly divergent lineage SARS-CoV-2 (B.1.641). This one most lineages so far, with 76 mutations (including 37 previously associated non-human mammalian hosts). From set five complete two partial deer-derived genomes we applied phylogenomic, recombination, selection mutation spectrum analyses, which provided for shared ancestry mink-derived virus. Our analysis also revealed epidemiologically linked human infection. Taken together, our findings provide sustained deer-to-human transmission.

Language: Английский

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Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(8), P. 505 - 518

Published: March 7, 2022

The AID/APOBEC polynucleotide cytidine deaminases have historically been classified as either DNA mutators or RNA editors based on their first identified nucleic acid substrate preference. can generate functional diversity at antibody genes but also cause genomic instability in cancer. informational the transcriptome of innate immune cells, and cancer cells. Members both classes act antiviral restriction factors. Recent structural work has illuminated differences similarities between enzymes that catalyse mutation, editing both, suggesting strict classification members this family should be reconsidered. As many these employed for targeted genome (or transcriptome) editing, a more holistic understanding will help improve design therapeutically relevant programmable base editors. In Perspective, Pecori et al. provide an overview deaminase family, discussing key features, how they contribute to viral tumour evolution harnessed (potentially therapeutic) base-editing purposes.

Language: Английский

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SARS-CoV-2 one year on: evidence for ongoing viral adaptation

Journal of General Virology, Journal Year: 2021, Volume and Issue: 102(4)

Published: April 15, 2021

SARS-CoV-2 is thought to have originated in the human population from a zoonotic spillover event. Infection humans results variety of outcomes ranging asymptomatic cases disease COVID-19, which can significant morbidity and mortality, with over two million confirmed deaths worldwide as January 2021. Over year into pandemic, sequencing analysis has shown that variants are being selected virus continues circulate widely within population. The predominant drivers genetic variation single nucleotide polymorphisms (SNPs) caused by polymerase error, potential host factor driven RNA modification, insertion/deletions (indels) resulting discontinuous nature viral synthesis. While many mutations represent neutral ‘genetic drift’ or quickly died out, subset may be affecting traits such transmissibility, pathogenicity, range, antigenicity virus. In this review, we summarise current extent change SARS-CoV-2, particularly recently emerging concern, consider phenotypic consequences evolution impact future trajectory pandemic.

Language: Английский

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Mutation Rates and Selection on Synonymous Mutations in SARS-CoV-2

Genome Biology and Evolution, Journal Year: 2021, Volume and Issue: 13(5)

Published: April 22, 2021

The COVID-19 pandemic has seen an unprecedented response from the sequencing community. Leveraging sequence data more than 140,000 SARS-CoV-2 genomes, we study mutation rates and selective pressures affecting virus. Understanding processes effects of selection profound implications for viral evolution, vaccine design, tracking spread. We highlight address some common genome analysis pitfalls that can lead to inaccurate inference selection, such as ignoring skews in genetic code, not accounting recurrent mutations, assuming evolutionary equilibrium. find two particular rates, G →U C →U, are similarly elevated considerably higher all other causing majority mutations genome, possibly result APOBEC ROS activity. These also tend occur many times at same positions along global phylogeny (i.e., they very homoplasic). observe effect genomic context on but is overall limited. Although previous studies have suggested acting decrease U content synonymous sites, bring forward evidence suggesting opposite.

Language: Английский

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Phylogenetic and phylodynamic approaches to understanding and combating the early SARS-CoV-2 pandemic

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(9), P. 547 - 562

Published: April 22, 2022

Language: Английский

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Transmission of SARS-CoV-2 from humans to animals and potential host adaptation

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 27, 2022

Abstract SARS-CoV-2, the causative agent of COVID-19 pandemic, can infect a wide range mammals. Since its spread in humans, secondary host jumps SARS-CoV-2 from humans to multiple domestic and wild populations mammals have been documented. Understanding extent adaptation these animal hosts is critical for assessing threat that spillback animal-adapted into poses. We compare genomic landscapes isolated species profiling mutational biases indicative potentially different selective pressures animals. focus on viral genomes mink ( Neovison vison ) white-tailed deer Odocoileus virginianus which independent outbreaks driven by onward animal-to-animal transmission reported. identify five candidate mutations animal-specific (NSP9_G37E, Spike_F486L, Spike_N501T, Spike_Y453F, ORF3a_L219V), one (NSP3a_L1035F), though they appear confer minimal advantage human-to-human transmission. No considerable changes mutation rate or evolutionary trajectory has resulted circulation thus far. Our findings suggest was required following human-to-animal spillover, highlighting ‘generalist’ nature as mammalian pathogen.

Language: Английский

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The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Sept. 13, 2022

During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA arise from misincorporation by RNA-polymerases and modification host factors. Analysis sequence patients showed a strong bias toward C-to-U mutation, suggesting potential mutational role APOBEC cytosine deaminases possess broad anti-viral activity. We report the first experimental evidence demonstrating APOBEC3A, APOBEC1, APOBEC3G edit on specific sites to mutations. However, replication viral progeny production in Caco-2 cells are not inhibited expression these APOBECs. Instead, wild-type APOBEC3 greatly promotes replication/propagation, utilizes APOBEC-mediated for fitness evolution. Unlike random mutations, this study suggests predictability all possible genome APOBECs based UC/AC motifs genomic structure.

Language: Английский

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SARS-CoV-2 and innate immunity: the good, the bad, and the “goldilocks”

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 171 - 183

Published: Nov. 20, 2023

Abstract An ancient conflict between hosts and pathogens has driven the innate adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that be leveraged therapeutically. The humoral response to SARS-CoV-2 infection been focus intense research, role immune system received significantly less attention. Here, we review current knowledge various means employs evade defense systems. We consider immunity in vaccines phenomenon long COVID.

Language: Английский

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