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1.
Virol J ; 18(1): 89, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931105

RESUMO

BACKGROUND: A novel coronavirus (SARS-CoV-2) emerging has put global public health institutes on high alert. Little is known about the epidemiology and clinical characteristics of human coronaviruses infections in relation to infections with other respiratory viruses. METHODS: From February 2017 to December 2019, 3660 respiratory samples submitted to Zhejiang Children Hospital with acute respiratory symptoms were tested for four human coronaviruses RNA by a novel two-tube multiplex reverse transcription polymerase chain reaction assays. Samples were also screened for the occurrence of SARS-CoV-2 by reverse transcription-PCR analysis. RESULTS: Coronavirus RNAs were detected in 144 (3.93%) specimens: HCoV-HKU1 in 38 specimens, HCoV-NL63 in 62 specimens, HCoV-OC43 in 38 specimens and HCoV-229E in 8 specimens. Genomes for SARS-CoV-2 were absent in all specimens by RT-PCR analysis during the study period. The majority of HCoV infections occurred during fall months. No significant differences in gender, sample type, year were seen across species. 37.5 to 52.6% of coronaviruses detected were in specimens testing positive for other respiratory viruses. Phylogenic analysis identified that Zhejiang coronaviruses belong to multiple lineages of the coronaviruses circulating in other countries and areas. CONCLUSION: Common HCoVs may have annual peaks of circulation in fall months in the Zhejiang province, China. Genetic relatedness to the coronaviruses in other regions suggests further surveillance on human coronaviruses in clinical samples are clearly needed to understand their patterns of activity and role in the emergence of novel coronaviruses.


Assuntos
COVID-19/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Infecções Respiratórias/virologia , SARS-CoV-2/genética , Adolescente , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , COVID-19/complicações , COVID-19/genética , COVID-19/fisiopatologia , Criança , Pré-Escolar , China/epidemiologia , Coronavirus/genética , Coronavirus/isolamento & purificação , Coronavirus Humano 229E/genética , Coronavirus Humano 229E/isolamento & purificação , Coronavirus Humano NL63/genética , Coronavirus Humano NL63/isolamento & purificação , Coronavirus Humano OC43/genética , Coronavirus Humano OC43/isolamento & purificação , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Filogenia , Infecções Respiratórias/complicações , Infecções Respiratórias/etiologia , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/genética
2.
Adv Exp Med Biol ; 1318: 23-39, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33973170

RESUMO

The ongoing coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is highly contagious and fatal, posing a direct threat to human health and the global economy. Most strategies to prevent, control, and eradicate COVID-19 are established based on the specific characteristics of the pathogen. The quest for interruption and eradication of COVID-19 has moved research forward in understanding fundamental aspects of the virus genome, proteome, replication mechanisms, and virus-host interactions, which pave the way for the development of effective antiviral drugs and vaccines. This chapter provides an overview of recent progress in human coronavirus taxonomy, molecular features of the SARS-CoV-2 genome and proteome, and virus life cycle.


Assuntos
COVID-19 , Coronavirus , SARS-CoV-2 , Antivirais/uso terapêutico , Classificação , Coronavirus/genética , Coronavirus/patogenicidade , Genoma Viral/genética , Humanos
3.
Viruses ; 13(4)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915875

RESUMO

Coronavirus (CoV) spillover events from wildlife reservoirs can result in mild to severe human respiratory illness. These spillover events underlie the importance of detecting known and novel CoVs circulating in reservoir host species and determining CoV prevalence and distribution, allowing improved prediction of spillover events or where a human-reservoir interface should be closely monitored. To increase the likelihood of detecting all circulating genera and strains, we have modified primers published by Watanabe et al. in 2010 to generate a semi-nested pan-CoV PCR assay. Representatives from the four coronavirus genera (α-CoVs, ß-CoVs, γ-CoVs and δ-CoVs) were tested and all of the in-house CoVs were detected using this assay. After comparing both assays, we found that the updated assay reliably detected viruses in all genera of CoVs with high sensitivity, whereas the sensitivity of the original assay was lower. Our updated PCR assay is an important tool to detect, monitor and track CoVs to enhance viral surveillance in reservoir hosts.


Assuntos
Coronavirus/classificação , Coronavirus/genética , Coronavirus/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Animais , Animais Selvagens , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Genoma Viral , Especificidade de Hospedeiro , Humanos , Limite de Detecção , Pandemias , Filogenia , RNA Viral
4.
Viruses ; 13(4)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920821

RESUMO

Coronaviruses (CoV) are widely distributed pathogens of human and animals and can cause mild or severe respiratory and gastrointestinal disease. Antigenic and genetic similarity of some CoVs within the Betacoronavirus genus is evident. Therefore, for the first time in Slovenia, we investigated the genetic diversity of partial 390-nucleotides of RNA-dependent-RNA polymerase gene (RdRp) for 66 human (HCoV) and 24 bovine CoV (BCoV) positive samples, collected between 2010 and 2016 from human patients and cattle with respiratory disease. The characterized CoV strains belong to four different clusters, in three separate human clusters HCoV-HKU1 (n = 34), HCoV-OC43 (n = 31) and HCoV 229E (n = 1) and bovine grouping only as BCoVs (n = 24). BCoVs from cattle and HCoV-OC43 were genetically the most closely related and share 96.4-97.1% nucleotide and 96.9-98.5% amino acid identity.


Assuntos
Doenças dos Bovinos/virologia , Coronavirus/classificação , Coronavirus/genética , Animais , Bovinos , Doenças dos Bovinos/transmissão , Coronavirus Humano 229E/genética , Infecções por Coronavirus/transmissão , Coronavirus Humano OC43/genética , Coronavirus Bovino/genética , Feminino , Variação Genética , Humanos , Masculino , Eslovênia
5.
Mol Biol Rep ; 48(4): 3629-3635, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33893925

RESUMO

PCR Single-Strand Conformation Polymorphism is a method used to identify and detect mutations and is now well known for its many applications on living beings. This paper will discuss the experimental details, limitations and sensitivity of the PCR Single-Strand Conformation Polymorphism method in relation to all existing literature available to us until today. Genomic DNA extraction, PCR amplification and Single-Strand Conformation Polymorphism conditions (concentration of polyacrylamide slab gel electrophoresis, dissociation treatment of double- stranded DNA) and comparison with PCR Restriction Fragment Length Polymorphism are presented. Since its discovery in 1989, there have been many variations, innovations, and modifications of the method, which makes it very easy, safe, fast and for this reason widely applied in clinical diagnostic, forensic medicine, biochemical, veterinary, microbiological, food and environmental laboratories. One of the possible applications of the method is the diagnosis and identification of mutations in new strains of coronaviruses, because science needs more tools to tackle the problem of this pandemic. The PCR Single-Strand Conformation Polymorphism method can be applied in many cases provided that control samples are available and the required conditions of the method are achieved.


Assuntos
Reação em Cadeia da Polimerase/métodos , Polimorfismo Conformacional de Fita Simples , Animais , Coronavirus/classificação , Coronavirus/genética , Coronavirus/isolamento & purificação , Humanos , Tipagem Molecular/métodos , Patologia Molecular/métodos , Polimorfismo de Fragmento de Restrição , Análise de Sequência/métodos
6.
Viruses ; 13(4)2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804957

RESUMO

Several life-threatening viruses have recently appeared, including the coronavirus, infecting a variety of human and animal hosts and causing a range of diseases like human upper respiratory tract infections. They not only cause serious human and animal deaths, but also cause serious public health problems worldwide. Currently, seven species are known to infect humans, namely SARS-CoV-2, MERS-CoV, SARS-CoV, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1. The coronavirus nonstructural protein 16 (NSP16) structure is similar to the 5'-end capping system of mRNA used by eukaryotic hosts and plays a vital role in evading host immunity response and protects the nascent viral mRNA from degradation. NSP16 is also well-conserved among related coronaviruses and requires its binding partner NSP10 to activate its enzymatic activity. With the continued threat of viral emergence highlighted by human coronaviruses and SARS-CoV-2, mutant strains continue to appear, affecting the highly conserved NSP16: this provides a possible therapeutic approach applicable to any novel coronavirus. To this end, current information on the 2'-O-MTase activity mechanism, the differences between NSP16 and NSP10 in human coronaviruses, and the current potential prevention and treatment strategies related to NSP16 are summarized in this review.


Assuntos
Infecções por Coronavirus/virologia , Coronavirus/metabolismo , Metiltransferases/metabolismo , Proteínas não Estruturais Virais/metabolismo , Animais , COVID-19/virologia , Coronavirus/enzimologia , Coronavirus/genética , Humanos , Metiltransferases/genética , SARS-CoV-2/enzimologia , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteínas não Estruturais Virais/genética
7.
Viruses ; 13(3)2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800523

RESUMO

Torovirus (ToV) has recently been classified into the new family Tobaniviridae, although it belonged to the Coronavirus (CoV) family historically. ToVs are associated with enteric diseases in animals and humans. In contrast to CoVs, which are recognised as pathogens of veterinary and medical importance, little attention has been paid to ToVs because their infections are usually asymptomatic or not severe; for a long time, only one equine ToV could be propagated in cultured cells. However, bovine ToVs, which predominantly cause diarrhoea in calves, have been detected worldwide, leading to economic losses. Porcine ToVs have also spread globally; although they have not caused serious economic losses, coinfections with other pathogens can exacerbate their symptoms. In addition, frequent inter- or intra-recombination among ToVs can increase pathogenesis or unpredicted host adaptation. These findings have highlighted the importance of ToVs as pathogens and the need for basic ToV research. Here, we review recent progress in the study of ToV molecular biology including reverse genetics, focusing on the similarities and differences between ToVs and CoVs.


Assuntos
Infecções por Torovirus/virologia , Torovirus/fisiologia , Animais , Coronavirus/genética , Coronavirus/fisiologia , Infecções por Coronavirus/virologia , Humanos , Torovirus/genética
9.
Exp Mol Med ; 53(4): 537-547, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33864026

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global outbreak of a coronavirus disease (herein referred to as COVID-19). Other viruses in the same phylogenetic group have been responsible for previous regional outbreaks, including SARS and MERS. SARS-CoV-2 has a zoonotic origin, similar to the causative viruses of these previous outbreaks. The repetitive introduction of animal viruses into human populations resulting in disease outbreaks suggests that similar future epidemics are inevitable. Therefore, understanding the molecular origin and ongoing evolution of SARS-CoV-2 will provide critical insights for preparing for and preventing future outbreaks. A key feature of SARS-CoV-2 is its propensity for genetic recombination across host species boundaries. Consequently, the genome of SARS-CoV-2 harbors signatures of multiple recombination events, likely encompassing multiple species and broad geographic regions. Other regions of the SARS-CoV-2 genome show the impact of purifying selection. The spike (S) protein of SARS-CoV-2, which enables the virus to enter host cells, exhibits signatures of both purifying selection and ancestral recombination events, leading to an effective S protein capable of infecting human and many other mammalian cells. The global spread and explosive growth of the SARS-CoV-2 population (within human hosts) has contributed additional mutational variability into this genome, increasing opportunities for future recombination.


Assuntos
Evolução Biológica , SARS-CoV-2/fisiologia , Animais , COVID-19/virologia , Coronavirus/genética , Genoma Viral , Humanos , Mutação , Filogenia , Recombinação Genética , SARS-CoV-2/genética , Seleção Genética , Glicoproteína da Espícula de Coronavírus/genética
11.
Nat Commun ; 12(1): 1607, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707453

RESUMO

In recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the "down" conformation, indicating they are more prone to adopt the receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. We further identified critical residues in the RBD underlying different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes. These results collectively indicate that tight RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection.


Assuntos
COVID-19/virologia , Quirópteros/virologia , Coronavirus/química , Coronavirus/genética , Pangolins/virologia , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Sequência de Aminoácidos , Enzima de Conversão de Angiotensina 2/química , Animais , COVID-19/epidemiologia , COVID-19/transmissão , Microscopia Crioeletrônica , Evolução Molecular , Interações entre Hospedeiro e Microrganismos , Humanos , Modelos Moleculares , Pandemias , Domínios Proteicos , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Glicoproteína da Espícula de Coronavírus/ultraestrutura
12.
J Phys Chem Lett ; 12(10): 2691-2698, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33689357

RESUMO

Severe acute respiratory syndrome coronaviruses have unusually large RNA genomes replicated by a multiprotein complex containing an RNA-dependent RNA polymerase (RdRp). Exonuclease activity enables the RdRp complex to remove wrongly incorporated bases via proofreading, a process not utilized by other RNA viruses. However, it is unclear why the RdRp complex needs proofreading and what the associated trade-offs are. Here we investigate the interplay among the accuracy, speed, and energetic cost of proofreading in the RdRp complex using a kinetic model and bioinformatics analysis. We find that proofreading nearly optimizes the rate of functional virus production. However, we find that further optimization would lead to a significant increase in the proofreading cost. Unexpected importance of the cost minimization is further supported by other global analyses. We speculate that cost optimization could help avoid cell defense responses. Thus, proofreading is essential for the production of functional viruses, but its rate is limited by energy costs.


Assuntos
Coronavirus/genética , Modelos Teóricos , RNA Polimerase Dependente de RNA/metabolismo , Proteínas Virais/metabolismo , Coronavirus/metabolismo , Cinética , Replicação Viral
13.
Front Cell Infect Microbiol ; 11: 609160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732659

RESUMO

There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent dangerous coronaviruses are MERS-CoV, SARS-CoV, and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. In this study, we analyzed transcriptome of MERS-CoV, SARS-CoV, and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression with upregulation of TET genes. Upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation may lead to increased genome instability and enhanced expression of genes with readthrough from retrotransposons. Therefore, people with higher basal level of retrotransposon such as cancer patients and aged people may have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA. Thus, we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. In summary, we propose our hypothesis that coronavirus invades human cells and interacts with retrotransposon, eliciting more severe symptoms in patients with underlying diseases. In the treatment of patients with coronavirus infection, it may be necessary to pay more attention to the potential harm contributed by retrotransposon dysregulation.


Assuntos
Infecções por Coronavirus/virologia , Coronavirus/genética , Genoma Viral/genética , Retroelementos/genética , Transcriptoma , Linhagem Celular Tumoral , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Vírus da SARS/genética , SARS-CoV-2/genética
14.
Bol Med Hosp Infant Mex ; 78(1): 41-58, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33661875

RESUMO

Coronaviruses (CoV) are enveloped, plus-strand RNA viruses that have the largest known RNA genomes and infect birds and mammals, causing various diseases. Human coronaviruses (HCoVs) were first identified in the mid-1960s and have been known to cause enteric or respiratory infections. In the last two decades, three HCoVs have emerged, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initiated the ongoing pandemic. SARS-CoV-2 causes a respiratory illness that presents as a mild upper respiratory disease but may result in acute respiratory distress syndrome, multi-organ failure and can be fatal, especially when underlying comorbidities are present. Children account for a low percentage of coronavirus disease 2019 (COVID-19) cases, with seemingly less severe disease. Most pediatric patients present mild or moderate symptoms or are asymptomatic. However, some cases may be severe. Therefore, SARS-CoV-2 infection and COVID-19 in pediatric patients must be studied in detail. This review describes general features of the molecular biology of CoVs and virus-host interactions that may be implicated in the pathogenesis of SARS-CoV-2.


Assuntos
COVID-19/virologia , Infecções por Coronavirus/virologia , Coronavirus/genética , Animais , COVID-19/epidemiologia , Criança , Coronavirus/classificação , Coronavirus/isolamento & purificação , Infecções por Coronavirus/classificação , Infecções por Coronavirus/epidemiologia , Humanos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
15.
Virus Res ; 297: 198382, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33705799

RESUMO

Coronaviruses are a large group of RNA viruses that infect a wide range of animal species. The replication strategy of coronaviruses involves recombination and mutation events that lead to the possibility of cross-species transmission. The high plasticity of the viral receptor due to a continuous modification of the host species habitat may be the cause of cross-species transmission that can turn into a threat to other species including the human population. The successive emergence of highly pathogenic coronaviruses such as the Severe Acute Respiratory Syndrome (SARS) in 2003, the Middle East Respiratory Syndrome Coronavirus in 2012, and the recent SARS-CoV-2 has incentivized a number of studies on the molecular basis of the coronavirus and its pathogenesis. The high degree of interrelatedness between humans and wild and domestic animals and the modification of animal habitats by human urbanization, has favored new viral spreads. Hence, knowledge on the main clinical signs of coronavirus infection in the different hosts and the distinctive molecular characteristics of each coronavirus is essential to prevent the emergence of new coronavirus diseases. The coronavirus infections routinely studied in veterinary medicine must be properly recognized and diagnosed not only to prevent animal disease but also to promote public health.


Assuntos
Infecções por Coronavirus , Coronavirus , Especificidade de Hospedeiro , Zoonoses Virais , Animais , Coronavirus/química , Coronavirus/genética , Coronavirus/fisiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Genoma Viral , Humanos , Fases de Leitura Aberta , RNA Viral , Proteínas Virais , Estruturas Virais , Transcrição Viral , Zoonoses Virais/transmissão , Zoonoses Virais/virologia , Montagem de Vírus , Replicação Viral
16.
J Vet Sci ; 22(1): e12, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33522164

RESUMO

BACKGROUND: Bats have been considered natural reservoirs for several pathogenic human coronaviruses (CoVs) in the last two decades. Recently, a bat CoV was detected in the Republic of Korea; its entire genome was sequenced and reported to be genetically similar to that of the severe acute respiratory syndrome CoV (SARS-CoV). OBJECTIVES: The objective of this study was to compare the genetic sequences of SARS-CoV, SARS-CoV-2, and the two Korean bat CoV strains 16BO133 and B15-21, to estimate the likelihood of an interaction between the Korean bat CoVs and the human angiotensin-converting enzyme 2 (ACE2) receptor. METHODS: The phylogenetic analysis was conducted with the maximum-likelihood (ML) method using MEGA 7 software. The Korean bat CoVs receptor binding domain (RBD) of the spike protein was analyzed by comparative homology modeling using the SWISS-MODEL server. The binding energies of the complexes were calculated using PRODIGY and MM/GBGA. RESULTS: Phylogenetic analyses of the entire RNA-dependent RNA polymerase, spike regions, and the complete genome revealed that the Korean CoVs, along with SARS-CoV and SARS-CoV-2, belong to the subgenus Sarbecovirus, within BetaCoVs. However, the two Korean CoVs were distinct from SARS-CoV-2. Specifically, the spike gene of the Korean CoVs, which is involved in host infection, differed from that of SARS-CoV-2, showing only 66.8%-67.0% nucleotide homology and presented deletions within the RBD, particularly within regions critical for cross-species transmission and that mediate interaction with ACE2. Binding free energy calculation revealed that the binding affinity of Korean bat CoV RBD to hACE2 was drastically lower than that of SARS-CoV and SARS-CoV-2. CONCLUSIONS: These results suggest that Korean bat CoVs are unlikely to bind to the human ACE2 receptor.


Assuntos
Quirópteros/virologia , Coronavirus/genética , Vírus da SARS/genética , SARS-CoV-2/genética , Animais , Genes Virais/genética , Genoma Viral/genética , Genômica , Humanos , Funções Verossimilhança , Filogenia , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo , República da Coreia , Análise de Sequência de DNA , Homologia de Sequência , Glicoproteína da Espícula de Coronavírus/genética , Ligação Viral
17.
Onderstepoort J Vet Res ; 88(1): e1-e8, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33567843

RESUMO

Human coronaviruses are known respiratory pathogens associated with a range of respiratory illnesses, and there are considerable morbidity and hospitalisation amongst immune-compromised individuals of all age groups. The emergence of a highly pathogenic human coronavirus in China in 2019 has confirmed the long-held opinion that these viruses are important emerging and re-emerging pathogens. In this review article, we trace the discovery and emergence of coronaviruses (CoVs) over time since they were first reported. The review article will enrich our understanding on the host range, diversity and evolution, transmission of human CoVs and the threat posed by these viruses circulating in animal populations but overtime have spilled over to humans because of the increased proximity between humans and animals.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/virologia , Coronavirus/classificação , Animais , Coronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Surtos de Doenças , Especificidade de Hospedeiro , Humanos
18.
Viruses ; 13(2)2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525437

RESUMO

The establishment of selective colonies of potential vertebrate hosts for viruses would provide experimental models for the understanding of pathogen-host interactions. This paper briefly surveys the reasons to conduct such studies and how the results might provide information that could be applied to disease prevention activities.


Assuntos
Reservatórios de Doenças/virologia , Interações Hospedeiro-Patógeno , Animais , COVID-19/prevenção & controle , COVID-19/transmissão , COVID-19/virologia , Quirópteros/virologia , Coronavirus/classificação , Coronavirus/genética , Coronavirus/patogenicidade , Especificidade de Hospedeiro , Humanos , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Zoonoses/prevenção & controle , Zoonoses/virologia
19.
J Clin Invest ; 131(7)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33571169

RESUMO

SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , COVID-19/terapia , COVID-19/virologia , Coronavirus/imunologia , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/sangue , Especificidade de Anticorpos , Coronavirus/classificação , Coronavirus/genética , Reações Cruzadas , Doenças Endêmicas , Genoma Viral , Humanos , Imunização Passiva , Epitopos Imunodominantes/química , Epitopos Imunodominantes/genética , Epitopos Imunodominantes/imunologia , Modelos Moleculares , Pandemias , SARS-CoV-2/genética , Especificidade da Espécie , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
20.
Virology ; 556: 62-72, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33545556

RESUMO

Members of the APOBEC family of cytidine deaminases show antiviral activities in mammalian cells through lethal editing in the genomes of small DNA viruses, herpesviruses and retroviruses, and potentially those of RNA viruses such as coronaviruses. Consistent with the latter, APOBEC-like directional C→U transitions of genomic plus-strand RNA are greatly overrepresented in SARS-CoV-2 genome sequences of variants emerging during the COVID-19 pandemic. A C→U mutational process may leave evolutionary imprints on coronavirus genomes, including extensive homoplasy from editing and reversion at targeted sites and the occurrence of driven amino acid sequence changes in viral proteins. If sustained over longer periods, this process may account for the previously reported marked global depletion of C and excess of U bases in human seasonal coronavirus genomes. This review synthesizes the current knowledge on APOBEC evolution and function and the evidence of their role in APOBEC-mediated genome editing of SARS-CoV-2 and other coronaviruses.


Assuntos
Desaminases APOBEC/metabolismo , Coronavirus/genética , Evolução Molecular , Genoma Viral/genética , Edição de RNA , Desaminases APOBEC/química , Desaminases APOBEC/genética , Animais , Infecções por Coronavirus/virologia , Humanos , Mutação , SARS-CoV-2/genética
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