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Pierre J. Talbot - One of the best experts on this subject based on the ideXlab platform.
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Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43.
Journal of virology, 2018Co-Authors: Mathieu Dubé, Marc Desforges, Alain Le Coupanec, Alan H M Wong, James M. Rini, Pierre J. TalbotAbstract:Human Coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more severe pathologies. HCoVs are not always confined to the upper respiratory tract and can invade the central nervous system (CNS) under still unclear circumstances. HCoV-induced neuropathologies in Humans are difficult to diagnose early enough to allow therapeutic interventions. Making use of our already described animal model of HCoV neuropathogenesis, we describe the route of neuropropagation from the nasal cavity to the olfactory bulb and piriform cortex and then the brain stem. We identified neuron-to-neuron propagation as one underlying mode of virus spreading in cell culture. Our data demonstrate that both passive diffusion of released viral particles and axonal transport are valid propagation strategies used by the virus. We describe for the first time the presence along axons of viral platforms whose static dynamism is reminiscent of viral assembly sites. We further reveal that HCoV OC43 modes of propagation can be modulated by selected HCoV OC43 proteins and axonal transport. Our work, therefore, identifies processes that may govern the severity and nature of HCoV OC43 neuropathogenesis and will make possible the development of therapeutic strategies to prevent occurrences.IMPORTANCE Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in Humans, and the presence and persistence of Human Coronaviruses (HCoV) in Human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.
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The Acetyl-Esterase Activity of the Hemagglutinin-Esterase Protein of Human Coronavirus OC43 Strongly Enhances the Production of Infectious Virus
Journal of virology, 2013Co-Authors: Marc Desforges, Jessica Desjardins, Chengsheng Zhang, Pierre J. TalbotAbstract:Most betaCoronaviruses possess an hemagglutinin-esterase (HE) protein, which appears to play a role in binding to or release from the target cell. Since this HE protein possesses an acetyl-esterase activity that removes acetyl groups from O-acetylated sialic acid, a role as a receptor-destroying enzyme has been postulated. However, the precise function of HE and of its enzymatic activity remains poorly understood. Making use of neutralizing antibody and of molecular clones of recombinant Human Coronavirus OC43 (HCoV-OC43), our results suggest that the HE protein of this HCoV could be associated with infection of target cells and, most notably, is important in the production of infectious viral particles. Indeed, after transfecting BHK-21 cells with various cDNA infectious clones of HCoV-OC43, either lacking the HE protein or bearing an HE protein with a nonfunctional acetyl-esterase enzymatic activity, we were reproducibly unable to detect recombinant infectious viruses compared to the reference infectious HCoV-OC43 clone pBAC-OC43(FL). Complementation experiments, using BHK-21 cells expressing wild-type HE, either transiently or in a stable ectopic expression, demonstrate that this protein plays a very significant role in the production of infectious recombinant coronaviral particles that can subsequently more efficiently infect susceptible epithelial and neuronal cells. Even though the S protein is the main viral factor influencing Coronavirus infection of susceptible cells, our results taken together indicate that a functionally active HE protein enhances the infectious properties of HCoV-OC43 and contributes to efficient virus dissemination in cell culture.
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Neuroprotective Effect of Apolipoprotein D against Human Coronavirus OC43-Induced Encephalitis in Mice
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008Co-Authors: Sonia Do Carmo, Hélène Jacomy, Pierre J. Talbot, Eric RassartAbstract:Apolipoprotein D (apoD) is a lipocalin upregulated in the nervous system after injury or pathologies such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We previously demonstrated that apoD protects against neuropathology by controlling the level of peroxidated lipids. Here, we further investigated the biological function of apoD in a mouse model of acute encephalitis. Our results show that apoD transcript and protein are upregulated during acute encephalitis induced by the Human Coronavirus OC43 (HCoV-OC43) infection. The apoD upregulation coincides with glial activation, and its expression returns to normal levels when the virus is cleared, concomitantly to a resolved glial reactivity. In addition, the overexpression of Human apoD in the neurons of Thy-1/ApoD transgenic mice results in a threefold increase of the number of mice surviving to HCoV-OC43 infection. This increased survival rate is correlated with an upregulated glial activation associated with a limited innate immune response (cytokines, chemokines) and T-cell infiltration into infected brains. Moreover, the protection seems to be associated with a restricted phospholipase A2 activity. These data reveal a role for apoD in the regulation of inflammation and suggest that it protects from HCoV-OC43-induced encephalitis, most likely through the phospholipase A2 signaling pathways.
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Human Coronavirus OC43 infection induces chronic encephalitis leading to disabilities in balb c mice
Virology, 2006Co-Authors: Hélène Jacomy, Gabriela Fragoso, Guillermina Almazan, Walter E. Mushynski, Pierre J. TalbotAbstract:The notion that an infectious respiratory pathogen can damage the central nervous system (CNS) and lead to neurological disease was tested using a Human respiratory Coronavirus, the OC43 strain of Human Coronavirus (HCoV-OC43). First, primary cell cultures were used to determine the susceptibility of each type of neural cells to virus infection. Neurons were the target cells, undergoing degeneration during infection, in part due to apoptosis. Second, neuropathogenicity was investigated in susceptible mice. Intracerebral inoculation of HCoV-OC43 into BALB/c mice led to an acute encephalitis with neuronal cell death by necrosis and apoptosis. Infectious virus was apparently cleared from surviving animals, whereas viral RNA persisted for several months. Some of the animals surviving to acute encephalitis presented an abnormal limb clasping reflex and a decrease in motor activity starting several months post-infection. These results suggest that viral persistence could be associated with an increased neuronal degeneration leading to neuropathology and motor deficits in susceptible individuals.
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Recovery of a Neurovirulent Human Coronavirus OC43 from an Infectious cDNA Clone
Journal of virology, 2006Co-Authors: Julien R. St-jean, Marc Desforges, Hélène Jacomy, Fernando Almazán, Luis Enjuanes, Pierre J. TalbotAbstract:This study describes the assembly of a full-length cDNA clone of Human Coronavirus (HCoV)-OC43 in a bacterial artificial chromosome (BAC). The BAC containing the full-length infectious cDNA (pBAC-OC43(FL)) was assembled using a two-part strategy. The first step consisted in the introduction of each end of the viral genome into the BAC with accessory sequences allowing proper transcription. The second step consisted in the insertion of the whole HCoV-OC43 cDNA genome into the BAC. To produce recombinant viral particles, pBAC-OC43(FL) was transfected into BHK-21 cells. Recombinant virus displayed the same phenotypic properties as the wild-type virus, including infectious virus titers produced in cell culture and neurovirulence in mice.
P J Talbot - One of the best experts on this subject based on the ideXlab platform.
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Activation of glial cells by Human Coronavirus OC43 infection.
Journal of neuroimmunology, 2000Co-Authors: J A Edwards, F Denis, P J TalbotAbstract:Multiple sclerosis (MS) is an immune-mediated demyelinating disease that could be triggered by a viral infection. Coronaviruses induce an MS-like disease in rodents, are neuroinvasive in Humans and can infect primary cultures of Human astrocytes and microglia. Infection of the Human astrocytic cell line U-373MG by the OC43 strain of Human Coronavirus caused an upregulation of IL-6, TNF-alpha, and MCP-1 mRNA expression. This virus also modulated the activity of matrix metalloproteinases-2 and -9 and augmented nitric oxide production in both U-373MG cells and the Human microglial cell line CHME-5. Thus, a coronaviral infection of glial cells could lead to the production of inflammatory molecules that have been associated with central nervous system pathologies such as MS.
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Sequence and expression of the ns2 protein gene of Human Coronavirus OC43.
The Journal of general virology, 1995Co-Authors: P Labonté, S Mounir, P J TalbotAbstract:The complete nucleotide sequence of the ns2 gene of Human Coronavirus OC43 (HCV-OC43) was determined. Sequence analysis revealed an open reading frame that could encode a protein of 278 amino acids, with an estimated molecular mass of 32.2 kDa. Six potential phosphorylation sites are present but no sites of N-glycosylation were found. The amino acid sequence of the HCV-OC43 ns2 protein shows 92% identity with that of the Mebus strain of bovine Coronavirus (BCV). However, a stretch of nine consecutive amino acids near the C terminus is completely different, causing it to be very hydrophilic, which contrasts with the hydrophobic nature of this region in BCV. As shown by immunofluorescence with a monospecific antiserum, the ns2 protein was expressed in the cytoplasm of HCV-OC43-infected HRT-18 cells.
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Molecular characterization of the S protein gene of Human Coronavirus OC43.
The Journal of general virology, 1993Co-Authors: S Mounir, P J TalbotAbstract:The gene encoding the spike protein of the OC43 strain of Human Coronavirus (HCV-OC43) was cloned and sequenced. The complete nucleotide sequence revealed an open reading frame of 4062 nucleotides encoding a protein of 1353 amino acids with a predicted M(r) of 150,078. Structural features include 22 N-glycosylation sites, an N-terminal hydrophobic signal sequence of 17 amino acids, an hydrophilic cysteine-rich sequence of 35 amino acids near the C terminus, and a potential proteolytic cleavage site (RRSR) between amino acid residues 758 and 759, yielding S1 and S2 segments of 84,730 and 65,366 M(r), respectively. The predicted amino acid sequence of the spike protein of HCV-OC43 has 91% identity with that of the Mebus strain of bovine Coronavirus, revealing more sequence divergence in the putative bulbous part (S1) than in the predicted stem region (S2).
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Sequence analysis of the membrane protein gene of Human Coronavirus OC43 and evidence for O-glycosylation.
The Journal of general virology, 1992Co-Authors: S Mounir, P J TalbotAbstract:The gene encoding the membrane (M) protein of the OC43 strain of Human Coronavirus (HCV-OC43) was amplified by a reverse transcription-polymerase chain reaction of viral RNA with HCV-OC43- and bovine Coronavirus (BCV)-specific primers. The nucleotide sequence of the cloned 1.5 kb fragment revealed an open reading frame (ORF) of 690 nucleotides which was identified as the M protein gene from its homology to BCV. This ORF encodes a protein of 230 amino acids with an M(r) of 26416. The gene is preceded by the motif UCCAAAC, analogous to the consensus Coronavirus transcription initiation sequence. The M protein of HCV-OC43 shows features typical of all Coronavirus M proteins studied: a hydrophilic, presumably external N terminus including about 10% of the protein, and a potential N-glycosylation site followed by three major hydrophobic transmembrane domains. The amino acid sequence of the M protein of HCV-OC43 has 94% identity with that of the Mebus strain of BCV, and also contains six potential O-glycosylation sites in the exposed N-terminal domain. Indeed, the glycosylation of the M protein was not inhibited in the presence of tunicamycin, which is indicative of O-glycosylation, as previously reported for BCV and murine hepatitis virus. Virions released from tunicamycin-treated cells contained the M glycoprotein but were devoid of both peplomer (S) and haemagglutinin-esterase (HE) proteins. Thus, inhibition of the N-glycosylation of the S and HE structural proteins prevented their incorporation into progeny virions, an indication that they are dispensable for virion morphogenesis, unlike the M protein.
Kwokyung Yuen - One of the best experts on this subject based on the ideXlab platform.
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molecular epidemiology of Human Coronavirus OC43 reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination
Journal of Virology, 2011Co-Authors: Susanna K P Lau, Paul P Lee, Alan K L Tsang, Cyril C Y Yip, Herman Tse, Rodney A Lee, Y L Lau, Kwokhung Chan, Patrick C Y Woo, Kwokyung YuenAbstract:Although Human Coronavirus OC43-OC43 (HCoV-OC43) is the Coronavirus most commonly associated with Human infections, little is known about its molecular epidemiology and evolution. We conducted a molecular epidemiology study to investigate different genotypes and potential recombination in HCoV-OC43. Twenty-nine HCoV-OC43 strains from nasopharyngeal aspirates, collected from 2004 to 2011, were subjected to RNA-dependent RNA polymerase (RdRp), spike, and nucleocapsid gene analysis. Phylogenetic analysis showed at least three distinct clusters of HCoV-OC43, although 10 unusual strains displayed incongruent phylogenetic positions between RdRp and spike genes. This suggested the presence of four HCoV-OC43 genotypes (A to D), with genotype D most likely arising from recombination. The complete genome sequencing of two genotype C and D strains and bootscan analysis showed recombination events between genotypes B and C in the generation of genotype D. Of the 29 strains, none belonged to the more ancient genotype A, 5 from 2004 belonged to genotype B, 15 from 2004 to 2006 belonged to genotype C, and 1 from 2004 and all 8 from 2008 to 2011 belonged to the recombinant genotype D. Molecular clock analysis using spike and nucleocapsid genes dated the most recent common ancestor of all genotypes to the 1950s, genotype B and C to the 1980s, genotype B to the 1990s, and genotype C to the late 1990s to early 2000s, while the recombinant genotype D strains were detected as early as 2004. This represents the first study to describe natural recombination in HCoV-OC43 and the evolution of different genotypes over time, leading to the emergence of novel genotype D, which is associated with pneumonia in our elderly population.
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False-Positive Results in a Recombinant Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV) Nucleocapsid Enzyme-Linked Immunosorbent Assay Due to HCoV-OC43 and HCoV-229E Rectified by Western Blotting with Recombinant SARS-CoV Spike Po
Journal of clinical microbiology, 2004Co-Authors: Patrick C Y Woo, Susanna K P Lau, Kwokhung Chan, Beatrice H.l. Wong, Wai-ting Hui, Grace See-wai Kwan, Jsm Peiris, Robert B. Couch, Kwokyung YuenAbstract:Using paired serum samples obtained from patients with illness associated with increases in anti-Human Coronavirus OC43 (HCoV-OC43) or anti-HCoV-229E antibodies, we examined the possibility of false-positive results detected in a recombinant severe acute respiratory syndrome (SARS)-associated Coronavirus (SARS-CoV) nucleocapsid protein immunoglobulin G enzyme-linked immunosorbent assay (ELISA). Three of the 21 and 1 of the 7 convalescent-phase serum samples from persons with increases in antibodies against HCoV-OC43 and HCoV-229E, respectively, tested positive by the recombinant SARS-CoV nucleocapsid protein-based ELISA. None of these samples were found to contain a specific antibody in the recombinant SARS-CoV spike polypeptide-based Western blot assay.
Wassim Chehadeh - One of the best experts on this subject based on the ideXlab platform.
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pcr array profiling of antiviral genes in Human embryonic kidney cells expressing Human Coronavirus OC43 structural and accessory proteins
Archives of Virology, 2018Co-Authors: Meshal Beidas, Wassim ChehadehAbstract:Human Coronavirus OC43 (HCoV-OC43) is a respiratory virus that usually causes a common cold. However, it has the potential to cause severe infection in young children and immunocompromised adults. Both SARS-CoV and MERS-CoV were shown to express proteins with the potential to evade early innate immune responses. However, the ability of HCoV-OC43 to antagonise the intracellular antiviral defences has not yet been investigated. The potential role of the HCoV-OC43 structural (M and N) and accessory proteins (ns2a and ns5a) in the alteration of antiviral gene expression was investigated in this study. HCoV-OC43M, N, ns2a and ns5a proteins were expressed in Human embryonic kidney 293 (HEK-293) cells before challenge with Sendai virus. The Human Antiviral Response PCR array was used to profile the antiviral gene expression in HEK-293 cells. Over 30 genes were downregulated in the presence of one of the HCoV-OC43 proteins, e.g. genes representing mitogen-activated protein kinases, toll-like receptors, interferons, interleukins, and signaling transduction proteins. Our findings suggest that similarly to SARS-CoV and MERS-CoV, HCoV-OC43 has the ability to downregulate the transcription of genes critical for the activation of different antiviral signaling pathways. Further studies are needed to confirm the role of HCoV-OC43 structural and accessory proteins in antagonising antiviral gene expression.
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Effect of Human Coronavirus OC43 Structural and Accessory Proteins on the Transcriptional Activation of Antiviral Response Elements.
Intervirology, 2018Co-Authors: Meshal Beidas, Wassim ChehadehAbstract:The molecular mechanisms underlying the pathogenesis of Human Coronavirus OC43 (HCoV-OC43) infection are poorly understood. In this study, we investigated the ability of HCoV-OC43 to antagonize the transcriptional activation of antiviral response elements. HCoV-OC43 structural (membrane M and nucleocapsid N) and accessory proteins (ns2a and ns5a) were expressed individually in Human embryonic kidney 293 (HEK-293) cells. The transcriptional activation of antiviral response elements was assessed by measuring the levels of firefly luciferase expressed under the control of interferon (IFN)-stimulated response element (ISRE), IFN-β promoter, or nuclear factor kappa B response element (NF-κB-RE). The antiviral gene expression profile in HEK-293 cells was determined by PCR array. The transcriptional activity of ISRE, IFN-β promoter, and NF-κB-RE was significantly reduced in the presence of HCoV-OC43 ns2a, ns5a, M, or N protein, following the challenge of cells with Sendai virus, IFN-α or tumor necrosis factor-α. The expression of antiviral genes involved in the type I IFN and NF-κB signaling pathways was also downregulated in the presence of HCoV-OC43 structural or accessory proteins. Both structural and accessory HCoV-OC43 proteins are able to inhibit antiviral response elements in HEK-293 cells, and to block the activation of different antiviral signaling pathways. © 2018 S. Karger AG, Basel.
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effect of Human Coronavirus OC43 structural and accessory proteins on the transcriptional activation of antiviral response elements
Intervirology, 2018Co-Authors: Meshal Beidas, Wassim ChehadehAbstract:Objectives: The molecular mechanisms underlying the pathogenesis of Human Coronavirus OC43 (HCoV-OC43) infection are poorly understood. In this study, we investigated the ability of HCoV-OC43 to antagonize the transcriptional activation of antiviral response elements. Methods: HCoV-OC43 structural (membrane M and nucleocapsid N) and accessory proteins (ns2a and ns5a) were expressed individually in Human embryonic kidney 293 (HEK-293) cells. The transcriptional activation of antiviral response elements was assessed by measuring the levels of firefly luciferase expressed under the control of interferon (IFN)-stimulated response element (ISRE), IFN-β promoter, or nuclear factor kappa B response element (NF-κB-RE). The antiviral gene expression profile in HEK-293 cells was determined by PCR array. Results: The transcriptional activity of ISRE, IFN-β promoter, and NF-κB-RE was significantly reduced in the presence of HCoV-OC43 ns2a, ns5a, M, or N protein, following the challenge of cells with Sendai virus, IFN-α or tumor necrosis factor-α. The expression of antiviral genes involved in the type I IFN and NF-κB signaling pathways was also downregulated in the presence of HCoV-OC43 structural or accessory proteins. Conclusion: Both structural and accessory HCoV-OC43 proteins are able to inhibit antiviral response elements in HEK-293 cells, and to block the activation of different antiviral signaling pathways.
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PCR Array Profiling of Antiviral Genes in Human Embryonic Kidney Cells Expressing Human Coronavirus OC43 Structural and Accessory Proteins
Open Forum Infectious Diseases, 2017Co-Authors: Meshal Beidas, Wassim ChehadehAbstract:Abstract Background Human Coronavirus OC43 (HCoV-OC43) causes common cold, and is associated with severe respiratory symptoms in infants, elderly and immunocompromised patients. HCoV-OC43 is a member of BetaCoronavirus genus that includes also the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) Coronaviruses. Both SARS-CoV and MERS-CoV were shown to express proteins with the potential to evade early innate immune responses. However, the ability of HCoV-OC43 to antagonise the intracellular antiviral defences has not yet been investigated. The objective of this study was to investigate the role of HCoV-OC43 structural (membrane and nucleocapsid) and accessory (ns5a and ns2a) proteins in the modulation of antiviral gene expression profile in Human embryonic kidney 293 (HEK-293) cells using PCR array analysis. Methods HCoV-OC43 membrane (M), nucleocapsid (N), ns5a and ns2a mRNA were amplified and cloned into the pAcGFP1-N expression vector (Clontech), followed by transfection in HEK-293 cells. Expression of M, N, ns5a and ns2a proteins were confirmed by indirect immunofluorescence test. Three days post-transfection, the cells were challenged by Sendai virus. The Human Antiviral Response PCR array system (Qiagen) was used to profile the antiviral gene expression in HEK-293 cells, using the fold regulation comparison and the manual normalisation methods. Results Around 50–60 genes were downregulated by HCoV-OC43 proteins, the most prominent genes being those critical for the activation of transcription factors involved in the antiviral response like interferon regulatory factors (IRFs) and activator protein 1 (AP-1). Among the most important downregulated genes were those coding for Interferons (IFNs) mitogen-activated protein kinases (MAPKs), pro-apoptotic and pyroptotic proteins (Caspases, cathepsins, tumour necrosis factor), pro-inflammatory cytokines (Interleukins), pattern recognition receptors (PRRs; toll-like receptors and NOD-like receptors) and their signaling transduction proteins (TICAM1, MAVS). Conclusion This study shows for the first time that similarly to SARS-CoV and MERS-CoV, HCoV-OC43 has the ability to downregulate the transcription of genes critical for the activation of different antiviral signaling pathways. Disclosures All authors: No reported disclosures.
Marc Van Ranst - One of the best experts on this subject based on the ideXlab platform.
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Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice
Antimicrobial agents and chemotherapy, 2009Co-Authors: Els Keyaerts, Leen Vijgen, Marc Van Ranst, Evelien Rysman, Jannick Verbeeck, Piet MaesAbstract:Until recently, Human Coronaviruses (HCoVs), such as HCoV strain OC43 (HCoV-OC43), were mainly known to cause 15 to 30% of mild upper respiratory tract infections. In recent years, the identification of new HCoVs, including severe acute respiratory syndrome Coronavirus, revealed that HCoVs can be highly pathogenic and can cause more severe upper and lower respiratory tract infections, including bronchiolitis and pneumonia. To date, no specific antiviral drugs to prevent or treat HCoV infections are available. We demonstrate that chloroquine, a widely used drug with well-known antimalarial effects, inhibits HCoV-OC43 replication in HRT-18 cells, with a 50% effective concentration (± standard deviation) of 0.306 ± 0.0091 μM and a 50% cytotoxic concentration (± standard deviation) of 419 ± 192.5 μM, resulting in a selectivity index of 1,369. Further, we investigated whether chloroquine could prevent HCoV-OC43-induced death in newborn mice. Our results show that a lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with chloroquine acquired transplacentally or via maternal milk. The highest survival rate (98.6%) of the pups was found when mother mice were treated daily with a concentration of 15 mg of chloroquine per kg of body weight. Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg chloroquine and 13% survival when treated with 1 mg/kg chloroquine. Our results show that chloroquine can be highly effective against HCoV-OC43 infection in newborn mice and may be considered as a future drug against HCoVs.
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Evolutionary History of the Closely Related Group 2 Coronaviruses: Porcine Hemagglutinating Encephalomyelitis Virus, Bovine Coronavirus, and Human Coronavirus OC43
Journal of virology, 2006Co-Authors: Leen Vijgen, Els Keyaerts, Philippe Lemey, Piet Maes, Kristien Van Reeth, Hans Nauwynck, Maurice Pensaert, Marc Van RanstAbstract:The close genetic and antigenic relatedness among the group 2 Coronaviruses Human Coronavirus OC43 (HCoV-OC43), bovine Coronavirus (BCoV), and porcine hemagglutinating encephalomyelitis virus (PHEV) suggests that these three viruses with different host specificities diverged fairly recently. In this study, we determined the complete genomic sequence of PHEV (strain PHEV-VW572), revealing the presence of a truncated group 2-specific ns2 gene in PHEV in comparison to other group 2 Coronaviruses. Using a relaxed molecular clock approach, we reconstructed the evolutionary relationships between PHEV, BCoV, and HCoV-OC43 in real-time units, which indicated relatively recent common ancestors for these species-specific Coronaviruses.
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Circulation of genetically distinct contemporary Human Coronavirus OC43 strains
Virology, 2005Co-Authors: Leen Vijgen, Els Keyaerts, Philippe Lemey, Elien Moës, Anne-mieke Vandamme, Marc Van RanstAbstract:In this study, we report the complete genome sequence of two contemporary Human Coronavirus OC43 (HCoV-OC43) strains detected in 2003 and 2004, respectively. Comparative genetic analyses of the circulating strains and the prototype HCoV-OC43 strain (ATCC VR759) were performed. Remarkably, a lower than expected similarity is found between the complete genomes and more in particular between the spike genes of the BE03 and BE04 strains. This finding suggests the existence of two genetically distinct HCoV-OC43 strains, circulating in Belgium in 2003 and 2004. Spike gene sequencing of three additional 2003 and two additional 2004 HCoV-OC43 strains, and subsequent phylogenetic analysis confirm this assumption. Compared to the ATCC prototype HCoV-OC43 strain, an important amino acid substitution is present in the potential cleavage site sequence of the spike protein of all contemporary strains, restoring the N-RRXRR-C motif, associated with increased spike protein cleavability in bovine Coronaviruses. We here describe specific characteristics associated with circulating HCoV-OC43 strains, and we provide substantial evidence for the genetic variability of HCoV-OC43.
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Complete genomic sequence of Human Coronavirus OC43: molecular clock analysis suggests a relatively recent zoonotic Coronavirus transmission event.
Journal of virology, 2005Co-Authors: Leen Vijgen, Els Keyaerts, Philippe Lemey, Elien Moës, Anne-mieke Vandamme, Inge Thoelen, Elke Wollants, Marc Van RanstAbstract:Coronaviruses are enveloped, positive-stranded RNA viruses with a genome of approximately 30 kb. Based on genetic similarities, Coronaviruses are classified into three groups. Two group 2 Coronaviruses, Human Coronavirus OC43 (HCoV-OC43) and bovine Coronavirus (BCoV), show remarkable antigenic and genetic similarities. In this study, we report the first complete genome sequence (30,738 nucleotides) of the prototype HCoV-OC43 strain (ATCC VR759). Complete genome and open reading frame (ORF) analyses were performed in comparison to the BCoV genome. In the region between the spike and membrane protein genes, a 290-nucleotide deletion is present, corresponding to the absence of BCoV ORFs ns4.9 and ns4.8. Nucleotide and amino acid similarity percentages were determined for the major HCoV-OC43 ORFs and for those of other group 2 Coronaviruses. The highest degree of similarity is demonstrated between HCoV-OC43 and BCoV in all ORFs with the exception of the E gene. Molecular clock analysis of the spike gene sequences of BCoV and HCoV-OC43 suggests a relatively recent zoonotic transmission event and dates their most recent common ancestor to around 1890. An evolutionary rate in the order of 4 x 10(-4) nucleotide changes per site per year was estimated. This is the first animal-Human zoonotic pair of Coronaviruses that can be analyzed in order to gain insights into the processes of adaptation of a nonHuman Coronavirus to a Human host, which is important for understanding the interspecies transmission events that led to the origin of the severe acute respiratory syndrome outbreak.