Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 96
Filter
1.
Front Public Health ; 10: 859900, 2022.
Article in English | MEDLINE | ID: covidwho-1776088
2.
Viruses ; 14(2)2022 02 21.
Article in English | MEDLINE | ID: covidwho-1705877

ABSTRACT

Recombination creates mosaic genomes containing regions with mixed ancestry, and the accumulation of such events over time can complicate greatly many aspects of evolutionary inference. Here, we developed a sliding window bootstrap (SWB) method to generate genomic bootstrap (GB) barcodes to highlight the regions supporting phylogenetic relationships. The method was applied to an alignment of 56 sarbecoviruses, including SARS-CoV and SARS-CoV-2, responsible for the SARS epidemic and COVID-19 pandemic, respectively. The SWB analyses were also used to construct a consensus tree showing the most reliable relationships and better interpret hidden phylogenetic signals. Our results revealed that most relationships were supported by just a few genomic regions and confirmed that three divergent lineages could be found in bats from Yunnan: SCoVrC, which groups SARS-CoV related coronaviruses from China; SCoV2rC, which includes SARS-CoV-2 related coronaviruses from Southeast Asia and Yunnan; and YunSar, which contains a few highly divergent viruses recently described in Yunnan. The GB barcodes showed evidence for ancient recombination between SCoV2rC and YunSar genomes, as well as more recent recombination events between SCoVrC and SCoV2rC genomes. The recombination and phylogeographic patterns suggest a strong host-dependent selection of the viral RNA-dependent RNA polymerase. In addition, SARS-CoV-2 appears as a mosaic genome composed of regions sharing recent ancestry with three bat SCoV2rCs from Yunnan (RmYN02, RpYN06, and RaTG13) or related to more ancient ancestors in bats from Yunnan and Southeast Asia. Finally, our results suggest that viral circular RNAs may be key molecules for the mechanism of recombination.


Subject(s)
DNA Barcoding, Taxonomic/methods , Disease Reservoirs/veterinary , Evolution, Molecular , Genomics/methods , Recombination, Genetic , SARS Virus/genetics , SARS-CoV-2/genetics , Animals , China , Chiroptera/virology , Disease Reservoirs/virology , Genome, Viral , Phylogeography
3.
Genome Biol Evol ; 14(2)2022 02 04.
Article in English | MEDLINE | ID: covidwho-1684680

ABSTRACT

The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2, and the large geographical distance between Wuhan and where the closest evolutionary related coronaviruses circulating in horseshoe bats (members of the Sarbecovirus subgenus) have been identified, is fueling speculation on the natural origins of SARS-CoV-2. We performed a comprehensive phylogenetic study on SARS-CoV-2 and all the related bat and pangolin sarbecoviruses sampled so far. Determining the likely recombination events reveals a highly reticulate evolutionary history within this group of coronaviruses. Distribution of the inferred recombination events is nonrandom with evidence that Spike, the main target for humoral immunity, is beside a recombination hotspot likely driving antigenic shift events in the ancestry of bat sarbecoviruses. Coupled with the geographic ranges of their hosts and the sampling locations, across southern China, and into Southeast Asia, we confirm that horseshoe bats, Rhinolophus, are the likely reservoir species for the SARS-CoV-2 progenitor. By tracing the recombinant sequence patterns, we conclude that there has been relatively recent geographic movement and cocirculation of these viruses' ancestors, extending across their bat host ranges in China and Southeast Asia over the last 100 years. We confirm that a direct proximal ancestor to SARS-CoV-2 has not yet been sampled, since the closest known relatives collected in Yunnan shared a common ancestor with SARS-CoV-2 approximately 40 years ago. Our analysis highlights the need for dramatically more wildlife sampling to: 1) pinpoint the exact origins of SARS-CoV-2's animal progenitor, 2) the intermediate species that facilitated transmission from bats to humans (if there is one), and 3) survey the extent of the diversity in the related sarbecoviruses' phylogeny that present high risk for future spillovers.


Subject(s)
Chiroptera/virology , Coronavirus/genetics , Pangolins/virology , Phylogeny , Recombination, Genetic , Animals , Humans , Phylogeography
4.
Mol Biol Evol ; 39(2)2022 02 03.
Article in English | MEDLINE | ID: covidwho-1672234

ABSTRACT

The evolutionary process of genetic recombination has the potential to rapidly change the properties of a viral pathogen, and its presence is a crucial factor to consider in the development of treatments and vaccines. It can also significantly affect the results of phylogenetic analyses and the inference of evolutionary rates. The detection of recombination from samples of sequencing data is a very challenging problem and is further complicated for SARS-CoV-2 by its relatively slow accumulation of genetic diversity. The extent to which recombination is ongoing for SARS-CoV-2 is not yet resolved. To address this, we use a parsimony-based method to reconstruct possible genealogical histories for samples of SARS-CoV-2 sequences, which enables us to pinpoint specific recombination events that could have generated the data. We propose a statistical framework for disentangling the effects of recurrent mutation from recombination in the history of a sample, and hence provide a way of estimating the probability that ongoing recombination is present. We apply this to samples of sequencing data collected in England and South Africa and find evidence of ongoing recombination.


Subject(s)
COVID-19 , SARS-CoV-2 , Genome, Viral , Humans , Mutation , Phylogeny , Recombination, Genetic
5.
Emerg Microbes Infect ; 11(1): 552-555, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1655962

ABSTRACT

We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the Orf1ab and Spike genes was found.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Recombination, Genetic , Spike Glycoprotein, Coronavirus/genetics
7.
Nature ; 603(7902): 679-686, 2022 03.
Article in English | MEDLINE | ID: covidwho-1638766

ABSTRACT

The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, while the second and third waves were driven by the Beta (B.1.351) and Delta (B.1.617.2) variants, respectively1-3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron, B.1.1.529) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, which are predicted to influence antibody neutralization and spike function4. Here we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Immune Evasion , SARS-CoV-2/isolation & purification , Antibodies, Neutralizing/immunology , Botswana/epidemiology , COVID-19/immunology , COVID-19/transmission , Humans , Models, Molecular , Mutation , Phylogeny , Recombination, Genetic , SARS-CoV-2/classification , SARS-CoV-2/immunology , South Africa/epidemiology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
8.
Mol Biol Evol ; 39(1)2022 01 07.
Article in English | MEDLINE | ID: covidwho-1635982

ABSTRACT

Coronaviruses (CoVs) have very large RNA viral genomes with a distinct genomic architecture of core and accessory open reading frames (ORFs). It is of utmost importance to understand their patterns and limits of homologous and nonhomologous recombination, because such events may affect the emergence of novel CoV strains, alter their host range, infection rate, tissue tropism pathogenicity, and their ability to escape vaccination programs. Intratypic recombination among closely related CoVs of the same subgenus has often been reported; however, the patterns and limits of genomic exchange between more distantly related CoV lineages (intertypic recombination) need further investigation. Here, we report computational/evolutionary analyses that clearly demonstrate a substantial ability for CoVs of different subgenera to recombine. Furthermore, we show that CoVs can obtain-through nonhomologous recombination-accessory ORFs from core ORFs, exchange accessory ORFs with different CoV genera, with other viruses (i.e., toroviruses, influenza C/D, reoviruses, rotaviruses, astroviruses) and even with hosts. Intriguingly, most of these radical events result from double crossovers surrounding the Spike ORF, thus highlighting both the instability and mobile nature of this genomic region. Although many such events have often occurred during the evolution of various CoVs, the genomic architecture of the relatively young SARS-CoV/SARS-CoV-2 lineage so far appears to be stable.


Subject(s)
Coronavirus/genetics , Genome, Viral , Recombination, Genetic , Spike Glycoprotein, Coronavirus/genetics , Open Reading Frames , Phylogeny
9.
Viruses ; 14(2)2022 01 18.
Article in English | MEDLINE | ID: covidwho-1625960

ABSTRACT

Bats have been recognized as an exceptional viral reservoir, especially for coronaviruses. At least three bat zoonotic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) have been shown to cause severe diseases in humans and it is expected more will emerge. One of the major features of CoVs is that they are all highly prone to recombination. An extreme example is the insertion of the P10 gene from reoviruses in the bat CoV GCCDC1, first discovered in Rousettus leschenaultii bats in China. Here, we report the detection of GCCDC1 in four different bat species (Eonycteris spelaea, Cynopterus sphinx, Rhinolophus shameli and Rousettus sp.) in Cambodia. This finding demonstrates a much broader geographic and bat species range for this virus and indicates common cross-species transmission. Interestingly, one of the bat samples showed a co-infection with an Alpha CoV most closely related to RsYN14, a virus recently discovered in the same genus (Rhinolophus) of bat in Yunnan, China, 2020. Taken together, our latest findings highlight the need to conduct active surveillance in bats to assess the risk of emerging CoVs, especially in Southeast Asia.


Subject(s)
Chiroptera/virology , Coronaviridae Infections/veterinary , Coronaviridae/classification , Coronaviridae/genetics , Disease Reservoirs/veterinary , Disease Reservoirs/virology , Phylogeography , Recombination, Genetic , Animals , Cambodia/epidemiology , China/epidemiology , Chiroptera/classification , Coronaviridae/isolation & purification , Coronaviridae Infections/epidemiology , Coronaviridae Infections/transmission , Evolution, Molecular , Genome, Viral , Phylogeny
10.
Emerg Microbes Infect ; 11(1): 168-171, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1623181

ABSTRACT

HCoV-OC43 is one of the mildly pathogenic coronaviruses with high infection rates in common population. Here, 43 HCoV-OC43 related cases with pneumonia were reported, corresponding genomes of HCoV-OC43 were obtained. Phylogenetic analyses based on complete genome, orf1ab and spike genes revealed that two novel genotypes of HCoV-OC43 have emerged in China. Obvious recombinant events also can be detected in the analysis of the evolutionary dynamics of novel HCoV-OC43 genotypes. Estimated divergence time analysis indicated that the two novel genotypes had apparently independent evolutionary routes. Efforts should be conducted for further investigation of genomic diversity and evolution analysis of mildly pathogenic coronaviruses.


Subject(s)
Common Cold/epidemiology , Coronavirus Infections/epidemiology , Coronavirus OC43, Human/genetics , Genome, Viral , Genotype , Pneumonia, Viral/epidemiology , Base Sequence , Bayes Theorem , Child , Child, Hospitalized , Child, Preschool , China/epidemiology , Common Cold/pathology , Common Cold/transmission , Common Cold/virology , Coronavirus Infections/pathology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Coronavirus OC43, Human/classification , Coronavirus OC43, Human/pathogenicity , Epidemiological Monitoring , Female , Humans , Infant , Male , Monte Carlo Method , Mutation , Phylogeny , Pneumonia, Viral/pathology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Recombination, Genetic
11.
Viruses ; 14(1)2022 01 09.
Article in English | MEDLINE | ID: covidwho-1611142

ABSTRACT

We found and genetically described two novel SARS-like coronaviruses in feces and oral swabs of the greater (R. ferrumequinum) and the lesser (R. hipposideros) horseshoe bats in southern regions of Russia. The viruses, named Khosta-1 and Khosta-2, together with related viruses from Bulgaria and Kenya, form a separate phylogenetic lineage. We found evidence of recombination events in the evolutionary history of Khosta-1, which involved the acquisition of the structural proteins S, E, and M, as well as the nonstructural genes ORF3, ORF6, ORF7a, and ORF7b, from a virus that is related to the Kenyan isolate BtKY72. The examination of bats by RT-PCR revealed that 62.5% of the greater horseshoe bats in one of the caves were positive for Khosta-1 virus, while its overall prevalence was 14%. The prevalence of Khosta-2 was 1.75%. Our results show that SARS-like coronaviruses circulate in horseshoe bats in the region, and we provide new data on their genetic diversity.


Subject(s)
Chiroptera/virology , SARS Virus/genetics , Animals , Base Sequence , Chiroptera/classification , Evolution, Molecular , Feces/virology , Metagenomics , Mouth/virology , Phylogeny , Prevalence , Recombination, Genetic , Russia , SARS Virus/classification , Species Specificity , Spike Glycoprotein, Coronavirus/genetics , Viral Proteins/genetics
12.
Viruses ; 14(1)2022 01 02.
Article in English | MEDLINE | ID: covidwho-1580394

ABSTRACT

Coronaviruses (CoVs) constitute a large and diverse subfamily of positive-sense single-stranded RNA viruses. They are found in many mammals and birds and have great importance for the health of humans and farm animals. The current SARS-CoV-2 pandemic, as well as many previous epidemics in humans that were of zoonotic origin, highlights the importance of studying the evolution of the entire CoV subfamily in order to understand how novel strains emerge and which molecular processes affect their adaptation, transmissibility, host/tissue tropism, and patho non-homologous genicity. In this review, we focus on studies over the last two years that reveal the impact of point mutations, insertions/deletions, and intratypic/intertypic homologous and non-homologous recombination events on the evolution of CoVs. We discuss whether the next generations of CoV vaccines should be directed against other CoV proteins in addition to or instead of spike. Based on the observed patterns of molecular evolution for the entire subfamily, we discuss five scenarios for the future evolutionary path of SARS-CoV-2 and the COVID-19 pandemic. Finally, within this evolutionary context, we discuss the recently emerged Omicron (B.1.1.529) VoC.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Evolution, Molecular , SARS-CoV-2/genetics , Animals , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/prevention & control , Coronavirus/classification , Coronavirus/genetics , Coronavirus/immunology , Drug Design , Genome, Viral/genetics , Humans , Mutation , Recombination, Genetic , SARS-CoV-2/classification , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Vaccination , Viral Vaccines/immunology
13.
J Virol ; 96(3): e0183721, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1546443

ABSTRACT

Research activities with infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently permitted only under biosafety level 3 (BSL3) containment. Here, we report the development of a single-cycle infectious SARS-CoV-2 virus replicon particle (VRP) system with a luciferase and green fluorescent protein (GFP) dual reporter that can be safely handled in BSL2 laboratories to study SARS-CoV-2 biology. The spike (S) gene of SARS-CoV-2 encodes the envelope glycoprotein, which is essential for mediating infection of new host cells. Through deletion and replacement of this essential S gene with a luciferase and GFP dual reporter, we have generated a conditional SARS-CoV-2 mutant (ΔS-VRP) that produces infectious particles only in cells expressing a viral envelope glycoprotein of choice. Interestingly, we observed more efficient production of infectious particles in cells expressing vesicular stomatitis virus (VSV) glycoprotein G [ΔS-VRP(G)] than in cells expressing other viral glycoproteins, including S. We confirmed that infection from ΔS-VRP(G) is limited to a single round and can be neutralized by anti-VSV serum. In our studies with ΔS-VRP(G), we observed robust expression of both luciferase and GFP reporters in various human and murine cell types, demonstrating that a broad variety of cells can support intracellular replication of SARS-CoV-2. In addition, treatment of ΔS-VRP(G)-infected cells with either of the anti-CoV drugs remdesivir (nucleoside analog) and GC376 (CoV 3CL protease inhibitor) resulted in a robust decrease in both luciferase and GFP expression in a drug dose- and cell-type-dependent manner. Taken together, our findings show that we have developed a single-cycle infectious SARS-CoV-2 VRP system that serves as a versatile platform to study SARS-CoV-2 intracellular biology and to perform high-throughput screening of antiviral drugs under BSL2 containment. IMPORTANCE Due to the highly contagious nature of SARS-CoV-2 and the lack of immunity in the human population, research on SARS-CoV-2 has been restricted to biosafety level 3 laboratories. This has greatly limited participation of the broader scientific community in SARS-CoV-2 research and thus has hindered the development of vaccines and antiviral drugs. By deleting the essential spike gene in the viral genome, we have developed a conditional mutant of SARS-CoV-2 with luciferase and fluorescent reporters, which can be safely used under biosafety level 2 conditions. Our single-cycle infectious SARS-CoV-2 virus replicon system can serve as a versatile platform to study SARS-CoV-2 intracellular biology and to perform high-throughput screening of antiviral drugs under BSL2 containment.


Subject(s)
Genetic Engineering , Recombination, Genetic , Replicon , SARS-CoV-2/genetics , COVID-19/virology , Cell Culture Techniques , Cell Line , Containment of Biohazards/standards , Genes, Reporter , Humans , Laboratories/standards , Viral Proteins/genetics , Virus Replication
14.
Mol Cell ; 81(21): 4467-4480.e7, 2021 11 04.
Article in English | MEDLINE | ID: covidwho-1473419

ABSTRACT

Viral RNA-dependent RNA polymerases (RdRps) are a target for broad-spectrum antiviral therapeutic agents. Recently, we demonstrated that incorporation of the T-1106 triphosphate, a pyrazine-carboxamide ribonucleotide, into nascent RNA increases pausing and backtracking by the poliovirus RdRp. Here, by monitoring enterovirus A-71 RdRp dynamics during RNA synthesis using magnetic tweezers, we identify the "backtracked" state as an intermediate used by the RdRp for copy-back RNA synthesis and homologous recombination. Cell-based assays and RNA sequencing (RNA-seq) experiments further demonstrate that the pyrazine-carboxamide ribonucleotide stimulates these processes during infection. These results suggest that pyrazine-carboxamide ribonucleotides do not induce lethal mutagenesis or chain termination but function by promoting template switching and formation of defective viral genomes. We conclude that RdRp-catalyzed intra- and intermolecular template switching can be induced by pyrazine-carboxamide ribonucleotides, defining an additional mechanistic class of antiviral ribonucleotides with potential for broad-spectrum activity.


Subject(s)
Pyrazines/chemistry , RNA Viruses/genetics , RNA, Viral/genetics , RNA-Dependent RNA Polymerase/genetics , Recombination, Genetic , Ribonucleotides/chemistry , Animals , Antiviral Agents , Catalysis , Cells, Cultured , Genetic Techniques , Genome , Genome, Viral , Homologous Recombination , Humans , Kinetics , Mice , Mice, Transgenic , Molecular Dynamics Simulation , Mutagenesis , Nucleotides/genetics , Protein Conformation , RNA/chemistry , RNA-Dependent RNA Polymerase/metabolism , RNA-Seq , Transgenes , Virulence
15.
Elife ; 102021 09 28.
Article in English | MEDLINE | ID: covidwho-1441361

ABSTRACT

High-throughput genomics of SARS-CoV-2 is essential to characterize virus evolution and to identify adaptations that affect pathogenicity or transmission. While single-nucleotide variations (SNVs) are commonly considered as driving virus adaption, RNA recombination events that delete or insert nucleic acid sequences are also critical. Whole genome targeting sequencing of SARS-CoV-2 is typically achieved using pairs of primers to generate cDNA amplicons suitable for next-generation sequencing (NGS). However, paired-primer approaches impose constraints on where primers can be designed, how many amplicons are synthesized and requires multiple PCR reactions with non-overlapping primer pools. This imparts sensitivity to underlying SNVs and fails to resolve RNA recombination junctions that are not flanked by primer pairs. To address these limitations, we have designed an approach called 'Tiled-ClickSeq', which uses hundreds of tiled-primers spaced evenly along the virus genome in a single reverse-transcription reaction. The other end of the cDNA amplicon is generated by azido-nucleotides that stochastically terminate cDNA synthesis, removing the need for a paired-primer. A sequencing adaptor containing a Unique Molecular Identifier (UMI) is appended to the cDNA fragment using click-chemistry and a PCR reaction generates a final NGS library. Tiled-ClickSeq provides complete genome coverage, including the 5'UTR, at high depth and specificity to the virus on both Illumina and Nanopore NGS platforms. Here, we analyze multiple SARS-CoV-2 isolates and clinical samples to simultaneously characterize minority variants, sub-genomic mRNAs (sgmRNAs), structural variants (SVs) and D-RNAs. Tiled-ClickSeq therefore provides a convenient and robust platform for SARS-CoV-2 genomics that captures the full range of RNA species in a single, simple assay.


Subject(s)
Base Sequence , Coronavirus/genetics , Genome, Viral , RNA , SARS-CoV-2/genetics , COVID-19/virology , DNA, Complementary , Gene Library , Genomics , High-Throughput Nucleotide Sequencing , Humans , Nanopores , Polymerase Chain Reaction , RNA, Messenger , RNA, Viral/genetics , Recombination, Genetic , Whole Genome Sequencing
16.
Int J Mol Sci ; 22(19)2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1438627

ABSTRACT

The ongoing pandemic coronavirus (CoV) disease 2019 (COVID-19) by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) has already caused substantial morbidity, mortality, and economic devastation. Reverse genetic approaches to generate recombinant viruses are a powerful tool to characterize and understand newly emerging viruses. To contribute to the global efforts for countermeasures to control the spread of SARS-CoV-2, we developed a passage-free SARS-CoV-2 clone based on a bacterial artificial chromosome (BAC). Moreover, using a Lambda-based Red recombination, we successfully generated different reporter and marker viruses, which replicated similar to a clinical isolate in a cell culture. Moreover, we designed a full-length reporter virus encoding an additional artificial open reading frame with wild-type-like replication features. The virus-encoded reporters were successfully applied to ease antiviral testing in cell culture models. Furthermore, we designed a new marker virus encoding 3xFLAG-tagged nucleocapsid that allows the detection of incoming viral particles and, in combination with bio-orthogonal labeling for the visualization of viral RNA synthesis via click chemistry, the spatiotemporal tracking of viral replication on the single-cell level. In summary, by applying BAC-based Red recombination, we developed a powerful, reliable, and convenient platform that will facilitate studies answering numerous questions concerning the biology of SARS-CoV-2.


Subject(s)
COVID-19/virology , Cloning, Molecular/methods , Genome, Viral , SARS-CoV-2/genetics , Animals , Chlorocebus aethiops , HEK293 Cells , Humans , Mutagenesis , Plasmids/genetics , Recombination, Genetic , Vero Cells
17.
Cell ; 184(20): 5179-5188.e8, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1401294

ABSTRACT

We present evidence for multiple independent origins of recombinant SARS-CoV-2 viruses sampled from late 2020 and early 2021 in the United Kingdom. Their genomes carry single-nucleotide polymorphisms and deletions that are characteristic of the B.1.1.7 variant of concern but lack the full complement of lineage-defining mutations. Instead, the remainder of their genomes share contiguous genetic variation with non-B.1.1.7 viruses circulating in the same geographic area at the same time as the recombinants. In four instances, there was evidence for onward transmission of a recombinant-origin virus, including one transmission cluster of 45 sequenced cases over the course of 2 months. The inferred genomic locations of recombination breakpoints suggest that every community-transmitted recombinant virus inherited its spike region from a B.1.1.7 parental virus, consistent with a transmission advantage for B.1.1.7's set of mutations.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Pandemics , Recombination, Genetic , SARS-CoV-2/genetics , Base Sequence/genetics , COVID-19/virology , Computational Biology/methods , Gene Frequency , Genome, Viral , Genotype , Humans , Mutation , Phylogeny , Polymorphism, Single Nucleotide , United Kingdom/epidemiology , Whole Genome Sequencing/methods
18.
PLoS Pathog ; 17(9): e1009814, 2021 09.
Article in English | MEDLINE | ID: covidwho-1394561

ABSTRACT

Many of us had refresher courses in virology, immunology, and epidemiology in 2020, and we were reminded of the fact that Homo sapiens, the wiliest predator on the planet, has been hunting everything that moves for millennia. These repeated interspecies contacts inherently lead to recurrent zoonosis (nonhuman to human) and anthroponosis (human to nonhuman). Given the accelerating changes in our ecosystems since the neolithic revolution, it was not surprising to see a virus that spreads via aerosolization and liquid droplets cause a pandemic in a few months. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic begs the question-which viruses could cause a global threat? In this Opinion, the characteristics that make adenoviruses a risk, which include efficient intra- and interspecies transmission, thermostable particles, persistent/latent infections in diverse hosts, and the ability to readily recombine and escape herd immunity, are discussed.


Subject(s)
Adenovirus Infections, Human/mortality , Pandemics/statistics & numerical data , Adenovirus Infections, Human/epidemiology , Animals , Human-Animal Interaction , Humans , Recombination, Genetic , Risk Factors , Species Specificity , Transcription, Genetic
19.
PLoS Genet ; 16(12): e1009272, 2020 12.
Article in English | MEDLINE | ID: covidwho-1388879

ABSTRACT

The Betacoronaviruses comprise multiple subgenera whose members have been implicated in human disease. As with SARS, MERS and now SARS-CoV-2, the origin and emergence of new variants are often attributed to events of recombination that alter host tropism or disease severity. In most cases, recombination has been detected by searches for excessively similar genomic regions in divergent strains; however, such analyses are complicated by the high mutation rates of RNA viruses, which can produce sequence similarities in distant strains by convergent mutations. By applying a genome-wide approach that examines the source of individual polymorphisms and that can be tested against null models in which recombination is absent and homoplasies can arise only by convergent mutations, we examine the extent and limits of recombination in Betacoronaviruses. We find that recombination accounts for nearly 40% of the polymorphisms circulating in populations and that gene exchange occurs almost exclusively among strains belonging to the same subgenus. Although experimental studies have shown that recombinational exchanges occur at random along the coronaviral genome, in nature, they are vastly overrepresented in regions controlling viral interaction with host cells.


Subject(s)
Betacoronavirus/classification , Betacoronavirus/genetics , Recombination, Genetic/genetics , Spike Glycoprotein, Coronavirus/genetics , Crossing Over, Genetic/genetics , Genes, Viral/genetics , Genome, Viral/genetics , Host Specificity/genetics , Models, Genetic , Polymorphism, Genetic , SARS-CoV-2/classification , SARS-CoV-2/genetics , Viral Tropism/genetics
20.
Cell Host Microbe ; 29(7): 1093-1110, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1385270

ABSTRACT

Humanity is currently facing the challenge of two devastating pandemics caused by two very different RNA viruses: HIV-1, which has been with us for decades, and SARS-CoV-2, which has swept the world in the course of a single year. The same evolutionary strategies that drive HIV-1 evolution are at play in SARS-CoV-2. Single nucleotide mutations, multi-base insertions and deletions, recombination, and variation in surface glycans all generate the variability that, guided by natural selection, enables both HIV-1's extraordinary diversity and SARS-CoV-2's slower pace of mutation accumulation. Even though SARS-CoV-2 diversity is more limited, recently emergent SARS-CoV-2 variants carry Spike mutations that have important phenotypic consequences in terms of both antibody resistance and enhanced infectivity. We review and compare how these mutational patterns manifest in these two distinct viruses to provide the variability that fuels their evolution by natural selection.


Subject(s)
HIV-1/genetics , Pandemics , SARS-CoV-2/genetics , COVID-19/immunology , Evolution, Molecular , Genome, Viral , Humans , Immune Evasion , Mutation , Receptors, Virus/genetics , Recombination, Genetic , Selection, Genetic , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Viral Proteins/chemistry , Viral Proteins/genetics
SELECTION OF CITATIONS
SEARCH DETAIL