Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 20
Filter
1.
J Virol ; 96(3): e0192821, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1691422

ABSTRACT

From 2014 to week 07/2020 the Centre for Health Protection in Hong Kong conducted screening for influenza C virus (ICV). A retrospective analysis of ICV detections to week 26/2019 revealed persistent low-level circulation with outbreaks occurring biennially in the winters of 2015 to 2016 and 2017 to 2018 (R. S. Daniels et al., J Virol 94:e01051-20, 2020, https://doi.org/10.1128/JVI.01051-20). Here, we report on an outbreak occurring in 2019 to 2020, reinforcing the observation of biennial seasonality in Hong Kong. All three outbreaks occurred in similar time frames, were subsequently dwarfed by seasonal epidemics of influenza types A and B, and were caused by similar proportions of C/Kanagawa/1/76 (K)-lineage and C/São Paulo/378/82 S1- and S2-sublineage viruses. Ongoing genetic drift was observed in all genes, with some evidence of amino acid substitution in the hemagglutinin-esterase-fusion (HEF) glycoprotein possibly associated with antigenic drift. A total of 61 ICV genomes covering the three outbreaks were analyzed for reassortment, and 9 different reassortant constellations were identified, 1 K-lineage, 4 S1-sublineage, and 4 S2-sublineage, with 6 of these being identified first in the 2019-1920 outbreak (2 S2-lineage and 4 S1-lineage). The roles that virus interference/enhancement, ICV persistent infection, genome evolution, and reassortment might play in the observed seasonality of ICV in Hong Kong are discussed. IMPORTANCE Influenza C virus (ICV) infection of humans is common, with the great majority of people being infected during childhood, though reinfection can occur throughout life. While infection normally results in "cold-like" symptoms, severe disease cases have been reported in recent years. However, knowledge of ICV is limited due to poor systematic surveillance and an inability to propagate the virus in large amounts in the laboratory. Following recent systematic surveillance in Hong Kong SAR, China, and direct ICV gene sequencing from clinical specimens, a 2-year cycle of disease outbreaks (epidemics) has been identified, with gene mixing playing a significant role in ICV evolution. Studies like those reported here are key to developing an understanding of the impact of influenza C virus infection in humans, notably where comorbidities exist and severe respiratory disease can develop.


Subject(s)
Disease Outbreaks , Influenza, Human/epidemiology , Influenza, Human/virology , Influenzavirus C/classification , Influenzavirus C/genetics , Reassortant Viruses , Hemagglutinins, Viral/chemistry , Hemagglutinins, Viral/genetics , Hong Kong/epidemiology , Humans , Models, Molecular , Mutation , Phylogeny , Public Health Surveillance , Sequence Analysis, DNA , Structure-Activity Relationship , Viral Fusion Proteins/chemistry , Viral Fusion Proteins/genetics
2.
Emerg Infect Dis ; 27(12): 3202-3205, 2021 12.
Article in English | MEDLINE | ID: covidwho-1613530

ABSTRACT

A case of human infection with influenza A(H1N1)pdm09 virus containing a nonstructural gene highly similar to Eurasian avian-like H1Nx swine influenza virus was detected in Denmark in January 2021. We describe the clinical case and report testing results of the genetic and antigenic characterizations of the virus.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Orthomyxoviridae Infections , Swine Diseases , Aged , Animals , Denmark/epidemiology , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Reassortant Viruses/genetics , Swine
3.
Transbound Emerg Dis ; 68(6): 3180-3186, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1532922

ABSTRACT

The first human case of zoonotic A(H7N4) avian influenza virus (AIV) infection was reported in early 2018 in China. Two months after this case, novel A(H7N4) viruses phylogenetically related to the Jiangsu isolate emerged in ducks from live bird markets in Cambodia. During active surveillance in Cambodia, a novel A(H7N6) reassortant of the zoonotic low pathogenic AIV (LPAIV) A(H7N4) was detected in domestic ducks at a slaughterhouse. Complete genome sequencing and phylogenetic analysis showed that the novel A(H7N6) AIV is a reassortant, in which four gene segments originated from Cambodia A(H7N4) viruses and four gene segments originated from LPAIVs in Eurasia. Animal infection experiments revealed that chickens transmitted the A(H7N6) virus via low-level direct contacts, but ducks did not. Although avian-origin A(H7Nx) LPAIVs do not contain the critical mammalian-adaptive substitution (E627K) in PB2, the lethality and morbidity of the A(H7N6) virus in BALB/c mice were similar to those of A(H7N9) viruses, suggesting potential for interspecies transmission. Our study reports the emergence of a new reassortant of zoonotic A(H7N4) AIVs with novel viral characteristics and emphasizes the need for ongoing surveillance of avian-origin A(H7Nx) viruses.


Subject(s)
Influenza A Virus, H7N9 Subtype , Influenza in Birds , Rodent Diseases , Animals , Cambodia/epidemiology , Chickens , China , Ducks , Influenza in Birds/epidemiology , Mice , Mice, Inbred BALB C , Phylogeny , Reassortant Viruses/genetics
5.
J Med Virol ; 93(10): 5998-6007, 2021 10.
Article in English | MEDLINE | ID: covidwho-1432442

ABSTRACT

In the context of the coronavirus disease 2019 pandemic, we investigated the epidemiological and clinical characteristics of a young patient infected by avian influenza A (H5N6) virus in Anhui Province, East China, and analyzed genomic features of the pathogen in 2020. Through the cross-sectional investigation of external environment monitoring (December 29-31, 2020), 1909 samples were collected from Fuyang City. It was found that the positive rate of H5N6 was higher than other areas obviously in Tianma poultry market, where the case appeared. In addition, dual coinfections were detected with a 0.057% polymerase chain reaction positive rate the surveillance years. The virus was the clade 2.3.4.4, which was most likely formed by genetic reassortment between H5N6 and H9N2 viruses. This study found that the evolution rates of the hemagglutinin and neuraminidase genes of the virus were higher than those of common seasonal influenza viruses. The virus was still highly pathogenic to poultry and had a preference for avian receptor binding.


Subject(s)
COVID-19/epidemiology , Influenza A virus/isolation & purification , Influenza in Birds/virology , Influenza, Human/virology , Animals , Child, Preschool , China , Female , Genome, Viral/genetics , Humans , Influenza A virus/classification , Influenza A virus/genetics , Influenza, Human/diagnosis , Mutation , Phylogeny , Poultry/virology , Reassortant Viruses/classification , Reassortant Viruses/genetics , Reassortant Viruses/isolation & purification , SARS-CoV-2 , Viral Proteins/genetics
6.
J Med Virol ; 93(10): 5998-6007, 2021 10.
Article in English | MEDLINE | ID: covidwho-1298504

ABSTRACT

In the context of the coronavirus disease 2019 pandemic, we investigated the epidemiological and clinical characteristics of a young patient infected by avian influenza A (H5N6) virus in Anhui Province, East China, and analyzed genomic features of the pathogen in 2020. Through the cross-sectional investigation of external environment monitoring (December 29-31, 2020), 1909 samples were collected from Fuyang City. It was found that the positive rate of H5N6 was higher than other areas obviously in Tianma poultry market, where the case appeared. In addition, dual coinfections were detected with a 0.057% polymerase chain reaction positive rate the surveillance years. The virus was the clade 2.3.4.4, which was most likely formed by genetic reassortment between H5N6 and H9N2 viruses. This study found that the evolution rates of the hemagglutinin and neuraminidase genes of the virus were higher than those of common seasonal influenza viruses. The virus was still highly pathogenic to poultry and had a preference for avian receptor binding.


Subject(s)
COVID-19/epidemiology , Influenza A virus/isolation & purification , Influenza in Birds/virology , Influenza, Human/virology , Animals , Child, Preschool , China , Female , Genome, Viral/genetics , Humans , Influenza A virus/classification , Influenza A virus/genetics , Influenza, Human/diagnosis , Mutation , Phylogeny , Poultry/virology , Reassortant Viruses/classification , Reassortant Viruses/genetics , Reassortant Viruses/isolation & purification , SARS-CoV-2 , Viral Proteins/genetics
7.
J Biol Chem ; 296: 100701, 2021.
Article in English | MEDLINE | ID: covidwho-1198856

ABSTRACT

The acid sphingomyelinase/ceramide system has been shown to be important for cellular infection with at least some viruses, for instance, rhinovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Functional inhibition of the acid sphingomyelinase using tricyclic antidepressants prevented infection of epithelial cells, for instance with SARS-CoV-2. The structure of ambroxol, that is, trans-4-[(2,4-dibromanilin-6-yl)-methyamino]-cyclohexanol, a mucolytic drug applied by inhalation, suggests that the drug might inhibit the acid sphingomyelinase and thereby infection with SARS-CoV-2. To test this, we used vesicular stomatitis virus pseudoviral particles presenting SARS-CoV-2 spike protein on their surface (pp-VSV-SARS-CoV-2 spike), a bona fide system for mimicking SARS-CoV-2 entry into cells. Viral uptake and formation of ceramide localization were determined by fluorescence microscopy, activity of the acid sphingomyelinase by consumption of [14C]sphingomyelin and ceramide was quantified by a kinase method. We found that entry of pp-VSV-SARS-CoV-2 spike required activation of acid sphingomyelinase and release of ceramide, events that were all prevented by pretreatment with ambroxol. We also obtained nasal epithelial cells from human volunteers prior to and after inhalation of ambroxol. Inhalation of ambroxol reduced acid sphingomyelinase activity in nasal epithelial cells and prevented pp-VSV-SARS-CoV-2 spike-induced acid sphingomyelinase activation, ceramide release, and entry of pp-VSV-SARS-CoV-2 spike ex vivo. The addition of purified acid sphingomyelinase or C16 ceramide restored entry of pp-VSV-SARS-CoV-2 spike into ambroxol-treated epithelial cells. We propose that ambroxol might be suitable for clinical studies to prevent coronavirus disease 2019.


Subject(s)
Ambroxol/pharmacology , Antiviral Agents/pharmacology , SARS-CoV-2/drug effects , Sphingomyelin Phosphodiesterase/genetics , Vesiculovirus/drug effects , Virus Internalization/drug effects , Administration, Inhalation , Animals , Biological Transport , Ceramides/metabolism , Chlorocebus aethiops , Drug Repositioning , Epithelial Cells/drug effects , Epithelial Cells/enzymology , Epithelial Cells/virology , Expectorants , Gene Expression , Humans , Primary Cell Culture , Reassortant Viruses/drug effects , Reassortant Viruses/physiology , SARS-CoV-2/physiology , Sphingomyelin Phosphodiesterase/antagonists & inhibitors , Sphingomyelin Phosphodiesterase/metabolism , Sphingomyelins/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , Vesiculovirus/physiology
8.
Viruses ; 13(1)2020 12 22.
Article in English | MEDLINE | ID: covidwho-1025055

ABSTRACT

Bats are often claimed to be a major source for future viral epidemics, as they are associated with several viruses with zoonotic potential. Here we describe the presence and biodiversity of bats associated with intensive pig farms devoted to the production of heavy pigs in northern Italy. Since chiropters or signs of their presence were not found within animal shelters in our study area, we suggest that fecal viruses with high environmental resistance have the highest likelihood for spillover through indirect transmission. In turn, we investigated the circulation of mammalian orthoreoviruses (MRVs), coronaviruses (CoVs) and astroviruses (AstVs) in pigs and bats sharing the same environment. Results of our preliminary study did not show any bat virus in pigs suggesting that spillover from these animals is rare. However, several AstVs, CoVs and MRVs circulated undetected in pigs. Among those, one MRV was a reassortant strain carrying viral genes likely acquired from bats. On the other hand, we found a swine AstV and a MRV strain carrying swine genes in bat guano, indicating that viral exchange at the bat-pig interface might occur more frequently from pigs to bats rather than the other way around. Considering the indoor farming system as the most common system in the European Union (EU), preventive measures should focus on biosecurity rather than displacement of bats, which are protected throughout the EU and provide critical ecosystem services for rural settings.


Subject(s)
Chiroptera , Swine , Animals , Biodiversity , Chiroptera/virology , DNA Viruses/classification , DNA Viruses/genetics , Ecosystem , Phylogeny , RNA Viruses/classification , RNA Viruses/genetics , Reassortant Viruses/genetics , Swine/virology , Swine Diseases/epidemiology , Swine Diseases/transmission , Swine Diseases/virology , Virus Diseases/veterinary
9.
BMC Genomics ; 22(1): 77, 2021 Jan 23.
Article in English | MEDLINE | ID: covidwho-1045026

ABSTRACT

BACKGROUND: Influenza viruses are dangerous pathogens. Seventy-Seven genomes of recently emerged genotype 4 reassortant Eurasian avian-like H1N1 virus (G4-EA-H1N1) are currently available. We investigated the presence and variation of potential G-quadruplex forming sequences (PQS), which can serve as targets for antiviral treatment. RESULTS: PQS were identified in all 77 genomes. The total number of PQS in G4-EA-H1N1 genomes was 571. Interestingly, the number of PQS per genome in individual close relative viruses varied from 4 to 12. PQS were not randomly distributed in the 8 segments of the G4-EA-H1N1 genome, the highest frequency of PQS being found in the NP segment (1.39 per 1000 nt), which is considered a potential target for antiviral therapy. In contrast, no PQS was found in the NS segment. Analyses of variability pointed the importance of some PQS; even if genome variation of influenza virus is extreme, the PQS with the highest G4Hunter score is the most conserved in all tested genomes. G-quadruplex formation in vitro was experimentally confirmed using spectroscopic methods. CONCLUSIONS: The results presented here hint several G-quadruplex-forming sequences in G4-EA-H1N1 genomes, that could provide good therapeutic targets.


Subject(s)
G-Quadruplexes , Influenza A Virus, H1N1 Subtype , Influenza, Human , Genome, Viral , Genotype , Humans , Influenza A Virus, H1N1 Subtype/genetics , Reassortant Viruses/genetics
10.
J Gen Virol ; 101(12): 1251-1260, 2020 12.
Article in English | MEDLINE | ID: covidwho-1066517

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged to cause widespread infections in humans. SARS-CoV-2 infections have been reported in the Kingdom of Saudi Arabia, where Middle East respiratory syndrome coronavirus (MERS-CoV) causes seasonal outbreaks with a case fatality rate of ~37 %. Here we show that there exists a theoretical possibility of future recombination events between SARS-CoV-2 and MERS-CoV RNA. Through computational analyses, we have identified homologous genomic regions within the ORF1ab and S genes that could facilitate recombination, and have analysed co-expression patterns of the cellular receptors for SARS-CoV-2 and MERS-CoV, ACE2 and DPP4, respectively, to identify human anatomical sites that could facilitate co-infection. Furthermore, we have investigated the likely susceptibility of various animal species to MERS-CoV and SARS-CoV-2 infection by comparing known virus spike protein-receptor interacting residues. In conclusion, we suggest that a recombination between SARS-CoV-2 and MERS-CoV RNA is possible and urge public health laboratories in high-risk areas to develop diagnostic capability for the detection of recombined coronaviruses in patient samples.


Subject(s)
Middle East Respiratory Syndrome Coronavirus/genetics , Reassortant Viruses , SARS-CoV-2/genetics , Animals , Base Sequence , Coinfection , Gene Expression Regulation, Viral , Genome, Viral , Host Specificity , Humans , Models, Molecular , Phylogeny , Protein Conformation , Receptors, Cell Surface , Recombination, Genetic , Viral Proteins/chemistry , Viral Proteins/genetics , Viral Proteins/metabolism
11.
Viruses ; 13(1)2021 Jan 16.
Article in English | MEDLINE | ID: covidwho-1040133

ABSTRACT

HIV-1 subtype CRF01_AE is the second most predominant strain in Bulgaria, yet little is known about the molecular epidemiology of its origin and transmissibility. We used a phylodynamics approach to better understand this sub-epidemic by analyzing 270 HIV-1 polymerase (pol) sequences collected from persons diagnosed with HIV/AIDS between 1995 and 2019. Using network analyses at a 1.5% genetic distance threshold (d), we found a large 154-member outbreak cluster composed mostly of persons who inject drugs (PWID) that were predominantly men. At d = 0.5%, which was used to identify more recent transmission, the large cluster dissociated into three clusters of 18, 12, and 7 members, respectively, five dyads, and 107 singletons. Phylogenetic analysis of the Bulgarian sequences with publicly available global sequences showed that CRF01_AE likely originated from multiple Asian countries, with Vietnam as the likely source of the outbreak cluster between 1988 and 1990. Our findings indicate that CRF01_AE was introduced into Bulgaria multiple times since 1988, and infections then rapidly spread among PWID locally with bridging to other risk groups and countries. CRF01_AE continues to spread in Bulgaria as evidenced by the more recent large clusters identified at d = 0.5%, highlighting the importance of public health prevention efforts in the PWID communities.


Subject(s)
Genotype , HIV Infections/epidemiology , HIV Infections/transmission , HIV Infections/virology , HIV-1/classification , HIV-1/genetics , Adolescent , Adult , Aged , Bulgaria/epidemiology , Female , Genetic Variation , HIV Infections/prevention & control , HIV-1/drug effects , Humans , Male , Middle Aged , Molecular Epidemiology , Phylogeny , Phylogeography , Public Health Surveillance , Reassortant Viruses , Recombination, Genetic , Young Adult
12.
Bioessays ; 43(3): e2000240, 2021 03.
Article in English | MEDLINE | ID: covidwho-927246

ABSTRACT

Severe acute respiratory syndrome-coronavirus (SARS-CoV)-2's origin is still controversial. Genomic analyses show SARS-CoV-2 likely to be chimeric, most of its sequence closest to bat CoV RaTG13, whereas its receptor binding domain (RBD) is almost identical to that of a pangolin CoV. Chimeric viruses can arise via natural recombination or human intervention. The furin cleavage site in the spike protein of SARS-CoV-2 confers to the virus the ability to cross species and tissue barriers, but was previously unseen in other SARS-like CoVs. Might genetic manipulations have been performed in order to evaluate pangolins as possible intermediate hosts for bat-derived CoVs that were originally unable to bind to human receptors? Both cleavage site and specific RBD could result from site-directed mutagenesis, a procedure that does not leave a trace. Considering the devastating impact of SARS-CoV-2 and importance of preventing future pandemics, researchers have a responsibility to carry out a thorough analysis of all possible SARS-CoV-2 origins.


Subject(s)
COVID-19/transmission , Genetic Engineering/ethics , Mutagenesis, Site-Directed/methods , Reassortant Viruses/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Base Sequence , COVID-19/pathology , COVID-19/virology , China , Chiroptera/virology , Eutheria/virology , Furin/metabolism , Humans , Protein Binding , Reassortant Viruses/metabolism , Reassortant Viruses/pathogenicity , Receptors, Virus/genetics , Receptors, Virus/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Sequence Alignment , Spike Glycoprotein, Coronavirus/metabolism
13.
Elife ; 92020 10 28.
Article in English | MEDLINE | ID: covidwho-895692

ABSTRACT

Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.


The new coronavirus, SARS-CoV-2, which causes the disease COVID-19, has had a serious worldwide impact on human health. The virus was virtually unknown at the beginning of 2020. Since then, intense research efforts have resulted in sequencing the coronavirus genome, identifying the structures of its proteins, and creating a wide range of tools to search for effective vaccines and therapies. Antibodies, which are immune molecules produced by the body that target specific segments of viral proteins can neutralize virus particles and trigger the immune system to kill cells infected with the virus. Several technologies are currently under development to exploit antibodies, including vaccines, blood plasma from patients who were previously infected, manufactured antibodies and more. The spike proteins on the surface of SARS-CoV-2 are considered to be prime antibody targets as they are accessible and have an essential role in allowing the virus to attach to and infect host cells. Antibodies bind to spike proteins and some can block the virus' ability to infect new cells. But some viruses, such as HIV and influenza, are able to mutate their equivalent of the spike protein to evade antibodies. It is unknown whether SARS-CoV-2 is able to efficiently evolve to evade antibodies in the same way. Weisblum, Schmidt et al. addressed this question using an artificial system that mimics natural infection in human populations. Human cells grown in the laboratory were infected with a hybrid virus created by modifying an innocuous animal virus to contain the SARS-CoV-2 spike protein, and treated with either manufactured antibodies or antibodies present in the blood of recovered COVID-19 patients. In this situation, only viruses that had mutated in a way that allowed them to escape the antibodies were able to survive. Several of the virus mutants that emerged had evolved spike proteins in which the segments targeted by the antibodies had changed, allowing these mutant viruses to remain undetected. An analysis of more than 50,000 real-life SARS-CoV-2 genomes isolated from patient samples further showed that most of these virus mutations were already circulating, albeit at very low levels in the infected human populations. These results show that SARS-CoV-2 can mutate its spike proteins to evade antibodies, and that these mutations are already present in some virus mutants circulating in the human population. This suggests that any vaccines that are deployed on a large scale should be designed to activate the strongest possible immune response against more than one target region on the spike protein. Additionally, antibody-based therapies that use two antibodies in combination should prevent the rise of viruses that are resistant to the antibodies and maintain the long-term effectiveness of vaccines and therapies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/therapy , Mutation , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal/immunology , Base Sequence , COVID-19/virology , Epitopes/genetics , Epitopes/immunology , Genes, Reporter , Humans , Immunization, Passive , Neutralization Tests , Protein Domains , Protein Isoforms/immunology , Reassortant Viruses/immunology , Receptors, Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Selection, Genetic , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vesiculovirus/genetics , Virus Replication
15.
Vet Microbiol ; 242: 108579, 2020 Mar.
Article in English | MEDLINE | ID: covidwho-826358

ABSTRACT

In China, variants of infectious bronchitis virus (IBV) evolve continually and diverse recombinant strains have been reported. Here, an IBV strain, designated as ck/CH/LJX/2017/07 (referred as JX17) was isolated from chicken vaccinated with H120 and 4/91 in Jiangxi, China, in 2017. Sequence analysis reveals of the S1 gene of JX17 the highest nucleotide identity of 98.15% with that of GI-7 genotype TW2575/98 strain. Furthermore, whole genome analysis among JX17 and other 18 IBV strains demonstrates that JX17 has the highest nucleotide identity of 95.94% with GI-19 genotype YX10 strain. Among all genes of JX17 except the S1 gene, the N gene and 3' UTR have the highest identity to GI-13 genotype 4/91 strain and the rest genes are the most identical to GI-19 genotype YX10 strain. Analyzed by the RDP and SimPlot, the recombination of JX17 strain was shown to occur in regions which include 5'-terminal S1 gene (20,344 to 22,447 nt), most N gene and 3' UTR (26,163 to 27,648 nt). The pathogenicity study shows that JX17 is a natural low virulent IBV variant which caused respiratory symptoms but no death. Taken together, these results indicate that IBV strains continue to evolve through genetic recombination and three prevalent genotypes in China including QX, TW and 4/91 have started to recombine.


Subject(s)
Coronavirus Infections/veterinary , Genome, Viral , Infectious bronchitis virus/genetics , Infectious bronchitis virus/pathogenicity , Reassortant Viruses/genetics , Recombination, Genetic , Animals , Chickens/virology , China , Coronavirus Infections/virology , Evolution, Molecular , Genotype , High-Throughput Nucleotide Sequencing , Infectious bronchitis virus/classification , Phylogeny , Poultry Diseases/virology , RNA, Viral/genetics , Reassortant Viruses/pathogenicity , Whole Genome Sequencing
16.
Med Sci (Paris) ; 36(8-9): 783-796, 2020.
Article in French | MEDLINE | ID: covidwho-706965

ABSTRACT

SARS-CoV-2 is a new human coronavirus (CoV), which emerged in People's Republic of China at the end of 2019 and is responsible for the global Covid-19 pandemic that caused more than 540 000 deaths in six months. Understanding the origin of this virus is an important issue and it is necessary to determine the mechanisms of its dissemination in order to be able to contain new epidemics. Based on phylogenetic inferences, sequence analysis and structure-function relationships of coronavirus proteins, informed by the knowledge currently available, we discuss the different scenarios evoked to account for the origin - natural or synthetic - of the virus. On the basis of currently available data, it is impossible to determine whether SARS-CoV-2 is the result of a natural zoonotic emergence or an accidental escape from experimental strains. Regardless of its origin, the study of the evolution of the molecular mechanisms involved in the emergence of this pandemic virus is essential to develop therapeutic and vaccine strategies.


TITLE: Retrouver les origines du SARS-CoV-2 dans les phylogénies de coronavirus. ABSTRACT: Le SARS-CoV-2 est un nouveau coronavirus (CoV) humain. Il a émergé en Chine fin 2019 et est responsable de la pandémie mondiale de Covid-19 qui a causé plus de 540 000 décès en six mois. La compréhension de l'origine de ce virus est une question importante et il est nécessaire de déterminer les mécanismes de sa dissémination afin de pouvoir se prémunir de nouvelles épidémies. En nous fondant sur des inférences phylogénétiques, l'analyse des séquences et les relations structure-fonction des protéines de coronavirus, éclairées par les connaissances actuellement disponibles, nous discutons les différents scénarios évoqués pour rendre compte de l'origine - naturelle ou synthétique - du virus.


Subject(s)
Betacoronavirus/genetics , Communicable Diseases, Emerging/virology , Coronavirus Infections/virology , Coronavirus/classification , Evolution, Molecular , Pandemics , Phylogeny , Pneumonia, Viral/virology , RNA, Viral/genetics , Amino Acid Sequence , Animals , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Biohazard Release , COVID-19 , China/epidemiology , Coronaviridae Infections/transmission , Coronaviridae Infections/veterinary , Coronaviridae Infections/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Reservoirs , Gain of Function Mutation , Genome, Viral , HIV/genetics , Host Specificity , Humans , Mammals/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Reassortant Viruses/genetics , SARS-CoV-2 , Sequence Alignment , Sequence Homology, Amino Acid , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/physiology , Zoonoses
17.
Mol Biol Evol ; 37(9): 2706-2710, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-641314

ABSTRACT

Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans. Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures. However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong. Here, we dispute the conclusions of Xia (2020. Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol. doi:10.1093/molbev/masa095) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor. We highlight major flaws in Xia's inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts. Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited.


Subject(s)
Alphacoronavirus/genetics , Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Genome, Viral , Pandemics , Pneumonia, Viral/epidemiology , Reassortant Viruses/genetics , Alphacoronavirus/classification , Alphacoronavirus/pathogenicity , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Biological Evolution , COVID-19 , Chiroptera/virology , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Coronavirus Infections/virology , CpG Islands , Dogs , Eutheria/virology , Humans , Immune Evasion/genetics , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Protein Binding , RNA, Viral/genetics , RNA, Viral/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/immunology , RNA-Binding Proteins/metabolism , Reassortant Viruses/classification , Reassortant Viruses/pathogenicity , SARS-CoV-2 , Virus Replication
18.
Mol Biol Evol ; 37(9): 2463-2464, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-638189

ABSTRACT

Identifying the origin of SARS-CoV-2, the etiological agent of the current COVID-19 pandemic, may help us to avoid future epidemics of coronavirus and other zoonoses. Several theories about the zoonotic origin of SARS-CoV-2 have recently been proposed. Although Betacoronavirus found in Rhinolophus bats from China have been broadly implicated, their genetic dissimilarity to SARS-CoV-2 is so high that they are highly unlikely to be its direct ancestors. Thus, an intermediary host is suspected to link bat to human coronaviruses. Based on genomic CpG dinucleotide patterns in different coronaviruses from different hosts, it was suggested that SARS-CoV-2 might have evolved in a canid gastrointestinal tract prior to transmission to humans. However, similar CpG patterns are now reported in coronaviruses from other hosts, including bats themselves and pangolins. Therefore, reduced genomic CpG alone is not a highly predictive biomarker, suggesting a need for additional biomarkers to reveal intermediate hosts or tissues. The hunt for the zoonotic origin of SARS-CoV-2 continues.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Genome, Viral , Pandemics , Pneumonia, Viral/epidemiology , Viral Proteins/genetics , Zoonoses/epidemiology , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , COVID-19 , Chiroptera/virology , Coronavirus Infections/transmission , Coronavirus Infections/virology , CpG Islands , Eutheria/virology , Evolution, Molecular , Gene Expression , Mutation , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Reassortant Viruses/classification , Reassortant Viruses/genetics , Reassortant Viruses/pathogenicity , Recombination, Genetic , SARS-CoV-2 , Viral Proteins/metabolism , Zoonoses/transmission , Zoonoses/virology
19.
Vopr Virusol ; 65(2): 62-70, 2020.
Article in Russian | MEDLINE | ID: covidwho-593172

ABSTRACT

Since the early 2000s, three novel zooanthroponous coronaviruses (Betacoronavirus) have emerged. The first outbreak of infection (SARS) caused by SARS-CoV virus occurred in the fall of 2002 in China (Guangdong Province). A second outbreak (MERS) associated with the new MERS-CoV virus appeared in Saudi Arabia in autumn 2012. The third epidemic, which turned into a COVID-19 pandemic caused by SARS-CoV-2 virus, emerged in China (Hubei Province) in the autumn 2019. This review focuses on ecological and genetic aspects that lead to the emergence of new human zoanthroponous coronaviruses. The main mechanism of adaptation of zoonotic betacoronaviruses to humans is to changes in the receptor-binding domain of surface protein (S), as a result of which it gains the ability to bind human cellular receptors of epithelial cells in respiratory and gastrointestinal tract. This process is caused by the high genetic diversity and variability combined with frequent recombination, during virus circulation in their natural reservoir - bats (Microchiroptera, Chiroptera). Appearance of SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS (subgenus Merbecovirus) viruses is a result of evolutionary events occurring in bat populations with further transfer of viruses to the human directly or through the intermediate vertebrate hosts, ecologically connected with bats. This review is based on the report at the meeting «Coronavirus - a global challenge to science¼ of the Scientific Council «Life Science¼ of the Russian Academy of Science: Lvov D.K., Alkhovsky S.V., Burtseva E.I. COVID-19 pandemic sources: origin, biology and genetics of coronaviruses of SARS-CoV, SARS-CoV-2, MERS-CoV (Conference hall of Presidium of RAS, 14 Leninsky Prospect, Moscow, Russia. April 16, 2020).


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Spike Glycoprotein, Coronavirus/genetics , Zoonoses/epidemiology , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , COVID-19 , Chiroptera/virology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Ecology , Evolution, Molecular , Gene Expression , Mutation , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phylogeny , Phylogeography , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Reassortant Viruses/classification , Reassortant Viruses/genetics , Reassortant Viruses/pathogenicity , Receptors, Virus/genetics , Receptors, Virus/metabolism , Recombination, Genetic , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Zoonoses/transmission , Zoonoses/virology
20.
Mol Biol Evol ; 37(9): 2699-2705, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-52538

ABSTRACT

Wild mammalian species, including bats, constitute the natural reservoir of betacoronavirus (including SARS, MERS, and the deadly SARS-CoV-2). Different hosts or host tissues provide different cellular environments, especially different antiviral and RNA modification activities that can alter RNA modification signatures observed in the viral RNA genome. The zinc finger antiviral protein (ZAP) binds specifically to CpG dinucleotides and recruits other proteins to degrade a variety of viral RNA genomes. Many mammalian RNA viruses have evolved CpG deficiency. Increasing CpG dinucleotides in these low-CpG viral genomes in the presence of ZAP consistently leads to decreased viral replication and virulence. Because ZAP exhibits tissue-specific expression, viruses infecting different tissues are expected to have different CpG signatures, suggesting a means to identify viral tissue-switching events. The author shows that SARS-CoV-2 has the most extreme CpG deficiency in all known betacoronavirus genomes. This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression. A survey of CpG deficiency in viral genomes identified a virulent canine coronavirus (alphacoronavirus) as possessing the most extreme CpG deficiency, comparable with that observed in SARS-CoV-2. This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG. Thus, viral surveys focused on decreasing CpG in viral RNA genomes may provide important clues about the selective environments and viral defenses in the original hosts.


Subject(s)
Alphacoronavirus/genetics , Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Genome, Viral , Pandemics , Pneumonia, Viral/epidemiology , Reassortant Viruses/genetics , Alphacoronavirus/classification , Alphacoronavirus/pathogenicity , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Biological Evolution , COVID-19 , Camelus/virology , Chiroptera/virology , Coronavirus Infections/immunology , Coronavirus Infections/transmission , Coronavirus Infections/virology , CpG Islands , Dogs , Hedgehogs/virology , Humans , Immune Evasion/genetics , Mice , Pneumonia, Viral/immunology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Protein Binding , RNA, Viral/genetics , RNA, Viral/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/immunology , RNA-Binding Proteins/metabolism , Rabbits , Rats , Reassortant Viruses/classification , Reassortant Viruses/pathogenicity , SARS-CoV-2 , Virus Replication
SELECTION OF CITATIONS
SEARCH DETAIL