- Human Coronaviruses: Respiratory Pathogens Revisited as Infectious Neuroinvasive, Neurotropic, and Neurovirulent Agents

2013 ◽  
pp. 114-143
Keyword(s):  
Respiratory Pathogens ◽  
Human Coronaviruses

scholarly journals Circulation of Respiratory Viruses in Hospitalized Adults before and during the COVID-19 Pandemic in Brescia, Italy: A Retrospective Study

2021 ◽  
Vol 18 (18) ◽  
pp. 9525
Author(s):  
Maria Antonia De Francesco ◽  
Caterina Pollara ◽  
Franco Gargiulo ◽  
Mauro Giacomelli ◽  
Arnaldo Caruso
Keyword(s):  
Respiratory Syncytial Virus ◽  
Influenza A ◽  
Statistical Significance ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Contact Tracing ◽  
Nucleic Acid Detection ◽  
Respiratory Pathogens ◽  
Syncytial Virus ◽  
Human Coronaviruses

Different preventive public health measures were adopted globally to limit the spread of SARS-CoV-2, such as hand hygiene and the use of masks, travel restrictions, social distance actions such as the closure of schools and workplaces, case and contact tracing, quarantine and lockdown. These measures, in particular physical distancing and the use of masks, might have contributed to containing the spread of other respiratory viruses that occurs principally by contact and droplet routes. The aim of this study was to evaluate the prevalence of different respiratory viruses (influenza viruses A and B, respiratory syncytial virus, parainfluenza viruses 1, 2, 3 and 4, rhinovirus, adenovirus, metapneumovirus and human coronaviruses) after one year of the pandemic. Furthermore, another aim was to evaluate the possible impact of these non-pharmaceutical measures on the circulation of seasonal respiratory viruses. This single center study was conducted between January 2017–February 2020 (pre-pandemic period) and March 2020–May 2021 (pandemic period). All adults >18 years with respiratory symptoms and tested for respiratory pathogens were included in the study. Nucleic acid detection of all respiratory viruses was performed by multiplex real time PCR. Our results show that the test positivity for influenza A and B, metapneumovirus, parainfluenza virus, respiratory syncytial virus and human coronaviruses decreased with statistical significance during the pandemic. Contrary to this, for adenovirus the decrease was not statistically significant. Conversely, a statistically significant increase was detected for rhinovirus. Coinfections between different respiratory viruses were observed during the pre-pandemic period, while the only coinfection detected during pandemic was between SARS-CoV-2 and rhinovirus. To understand how the preventive strategies against SARS-CoV-2 might alter the transmission dynamics and epidemic patterns of respiratory viruses is fundamental to guide future preventive recommendations.

scholarly journals Coronavirus hemagglutinin-esterase and spike proteins coevolve for functional balance and optimal virion avidity

2020 ◽  
Vol 117 (41) ◽  
pp. 25759-25770 ◽  
Author(s):  
Yifei Lang ◽  
Wentao Li ◽  
Zeshi Li ◽  
Danielle Koerhuis ◽  
Arthur C. S. van den Burg ◽  
...  
Keyword(s):  
Influenza A ◽  
Protein S ◽  
Respiratory Pathogens ◽  
Protein Species ◽  
Influenza A Viruses ◽  
Lectin Domain ◽  
Functional Balance ◽  
Worldwide Distribution ◽  
Animal Pathogens ◽  
Human Coronaviruses

Human coronaviruses OC43 and HKU1 are respiratory pathogens of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spillover. All three viruses attach to 9-O-acetylated sialoglycans via spike protein S with hemagglutinin-esterase (HE) acting as a receptor-destroying enzyme. In BCoV, an HE lectin domain promotes esterase activity toward clustered substrates. OC43 and HKU1, however, lost HE lectin function as an adaptation to humans. Replaying OC43 evolution, we knocked out BCoV HE lectin function and performed forced evolution-population dynamics analysis. Loss of HE receptor binding selected for second-site mutations in S, decreasing S binding affinity by orders of magnitude. Irreversible HE mutations led to cooperativity in virus swarms with low-affinity S minority variants sustaining propagation of high-affinity majority phenotypes. Salvageable HE mutations induced successive second-site substitutions in both S and HE. Apparently, S and HE are functionally interdependent and coevolve to optimize the balance between attachment and release. This mechanism of glycan-based receptor usage, entailing a concerted, fine-tuned activity of two envelope protein species, is unique among CoVs, but reminiscent of that of influenza A viruses. Apparently, general principles fundamental to virion–sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens.

scholarly journals Saliva is more sensitive for SARS-CoV-2 detection in COVID-19 patients than nasopharyngeal swabs

2020 ◽  
Author(s):  
Anne L. Wyllie ◽  
John Fournier ◽  
Arnau Casanovas-Massana ◽  
Melissa Campbell ◽  
Maria Tokuyama ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Large Scale ◽  
Diagnostic Testing ◽  
Detection Sensitivity ◽  
Respiratory Pathogens ◽  
Sample Collection ◽  
Diagnostic Approaches ◽  
Exposure Risks ◽  
Human Coronaviruses ◽  
Low Sensitivity

AbstractRapid and accurate SARS-CoV-2 diagnostic testing is essential for controlling the ongoing COVID-19 pandemic. The current gold standard for COVID-19 diagnosis is real-time RT-PCR detection of SARS-CoV-2 from nasopharyngeal swabs. Low sensitivity, exposure risks to healthcare workers, and global shortages of swabs and personal protective equipment, however, necessitate the validation of new diagnostic approaches. Saliva is a promising candidate for SARS-CoV-2 diagnostics because (1) collection is minimally invasive and can reliably be self-administered and (2) saliva has exhibited comparable sensitivity to nasopharyngeal swabs in detection of other respiratory pathogens, including endemic human coronaviruses, in previous studies. To validate the use of saliva for SARS-CoV-2 detection, we tested nasopharyngeal and saliva samples from confirmed COVID-19 patients and self-collected samples from healthcare workers on COVID-19 wards. When we compared SARS-CoV-2 detection from patient-matched nasopharyngeal and saliva samples, we found that saliva yielded greater detection sensitivity and consistency throughout the course of infection. Furthermore, we report less variability in self-sample collection of saliva. Taken together, our findings demonstrate that saliva is a viable and more sensitive alternative to nasopharyngeal swabs and could enable at-home self-administered sample collection for accurate large-scale SARS-CoV-2 testing.

scholarly journals Human Coronavirus HKU1 Spike Protein UsesO-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme

2015 ◽  
Vol 89 (14) ◽  
pp. 7202-7213 ◽  
Author(s):  
Xingchuan Huang ◽  
Wenjuan Dong ◽  
Aleksandra Milewska ◽  
Anna Golda ◽  
Yonghe Qi ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Viral Entry ◽  
Host Cells ◽  
Cellular Receptor ◽  
Respiratory Pathogens ◽  
Airway Epithelial ◽  
Human Coronavirus ◽  
Rd Cells ◽  
Human Coronaviruses

ABSTRACTHuman coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only one with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that is unique to the group a betacoronaviruses (group 2a). The function of HKU1-HE remains largely undetermined. In this study, we examined binding of the S1 domain of hCoV-HKU1 spike to a panel of cells and found that the S1 could specifically bind on the cell surface of a human rhabdomyosarcoma cell line, RD. Pretreatment of RD cells with neuraminidase (NA) and trypsin greatly reduced the binding, suggesting that the binding was mediated by sialic acids on glycoproteins. However, unlike other group 2a CoVs, e.g., hCoV-OC43, for which 9-O-acetylated sialic acid (9-O-Ac-Sia) serves as a receptor determinant, HKU1-S1 bound with neither 9-O-Ac-Sia-containing glycoprotein(s) nor rat and mouse erythrocytes. Nonetheless, the HKU1-HE was similar to OC43-HE, also possessed sialate-O-acetylesterase activity, and acted as a receptor-destroying enzyme (RDE) capable of eliminating the binding of HKU1-S1 to RD cells, whereas theO-acetylesterase-inactive HKU1-HE mutant lost this capacity. Using primary human ciliated airway epithelial (HAE) cell cultures, the onlyin vitroreplication model for hCoV-HKU1 infection, we confirmed that pretreatment of HAE cells with HE but not the enzymatically inactive mutant blocked hCoV-HKU1 infection. These results demonstrate that hCoV-HKU1 exploitsO-Ac-Sia as a cellular attachment receptor determinant to initiate the infection of host cells and that its HE protein possesses the corresponding sialate-O-acetylesterase RDE activity.IMPORTANCEHuman coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic acid moieties on glycoproteins are critical receptor determinants for the hCoV-HKU1 infection. Interestingly, the virus seems to employ a type of sialic acid different from those employed by other group 2a CoVs. In addition, we determined that the HKU1-HE protein is anO-acetylesterase and acts as a receptor-destroying enzyme (RDE) for hCoV-HKU1. This is the first study to demonstrate that hCoV-HKU1 uses certain types ofO-acetylated sialic acid residues on glycoproteins to initiate the infection of host cells and that the HKU1-HE protein possesses sialate-O-acetylesterase RDE activity.

scholarly journals Respiratory tract infections among French Hajj pilgrims from 2014 to 2017

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Van-Thuan Hoang ◽  
Saliha Ali-Salem ◽  
Khadidja Belhouchat ◽  
Mohammed Meftah ◽  
Doudou Sow ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Tract ◽  
Respiratory Symptoms ◽  
Respiratory Tract Infections ◽  
Influenza Viruses ◽  
Respiratory Pathogen ◽  
Respiratory Pathogens ◽  
Increased Risk ◽  
Human Coronaviruses ◽  
Tract Infections

AbstractRespiratory tract infections (RTIs) are common among Hajj pilgrims, but risk factors for RTIs and respiratory pathogen acquisition during the Hajj are not clearly identified. Based on previous studies, most frequent pathogens acquired by Hajj pilgrims were investigated: rhinovirus, human coronaviruses, influenza viruses, Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Haemophilus influenzae. 485 pilgrims were included. 82.1% presented with RTIs. Respiratory chronic diseases were associated with cough, Influenza-like illness (ILI) and the acquisition of H. influenzae. Vaccination against invasive pneumococcal diseases (IPD) and influenza was associated with a decrease in the acquisition of S. pneumoniae and prevalence of ILI (aRR = 0.53, 95%CI [0.39–0.73] and aRR = 0.69, 95%CI [0.52–0.92] respectively). Individuals carrying rhinovirus and H. influenzae-S. pneumoniae together were respectively twice and five times more likely to have respiratory symptoms. Individual with H. influenzae-K. pneumoniae carriage were twice (p = 0.04) as likely to develop a cough. The use of disposable handkerchiefs was associated with a decrease in the acquisition of S. aureus (aRR = 0.75, 95%CI [0.57–0.97]). Results could be used to identify pilgrims at increased risk of RTIs and acquisition of respiratory pathogens. Results also confirm the effectiveness of influenza and IPD vaccinations in reducing ILI symptoms and acquisition of S. pneumoniae carriage respectively.

scholarly journals Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A

2019 ◽  
Vol 116 (7) ◽  
pp. 2681-2690 ◽  
Author(s):  
Ruben J. G. Hulswit ◽  
Yifei Lang ◽  
Mark J. G. Bakkers ◽  
Wentao Li ◽  
Zeshi Li ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Receptor Binding ◽  
Protein S ◽  
Protein Domain ◽  
Spike Protein ◽  
Ligand Docking ◽  
Respiratory Pathogens ◽  
Receptor Binding Site ◽  
Human Coronaviruses

Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. OC43 is in fact a host-range variant of the species Betacoronavirus-1, and more closely related to bovine coronavirus (BCoV)—its presumptive ancestor—and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) and HKU1 employ glycan-based receptors carrying 9-O-acetylated sialic acid (9-O-Ac-Sia). Receptor binding is mediated by spike protein S, the main determinant of coronavirus host specificity. For BCoV, a crystal structure for the receptor-binding domain S1A is available and for HKU1 a cryoelectron microscopy structure of the complete S ectodomain. However, the location of the receptor-binding site (RBS), arguably the single-most important piece of information, is unknown. Here we solved the 3.0-Å crystal structure of PHEV S1A. We then took a comparative structural analysis approach to map the β1CoV S RBS, using the general design of 9-O-Ac-Sia-binding sites as blueprint, backed-up by automated ligand docking, structure-guided mutagenesis of OC43, BCoV, and PHEV S1A, and infectivity assays with BCoV-S–pseudotyped vesicular stomatitis viruses. The RBS is not exclusive to OC43 and related animal viruses, but is apparently conserved and functional also in HKU1 S1A. The binding affinity of the HKU1 S RBS toward short sialoglycans is significantly lower than that of OC43, which we attribute to differences in local architecture and accessibility, and which may be indicative for differences between the two viruses in receptor fine-specificity. Our findings challenge reports that would map the OC43 RBS elsewhere in S1A and that of HKU1 in domain S1B.

scholarly journals Neuroinvasion by Human Respiratory Coronaviruses

2000 ◽  
Vol 74 (19) ◽  
pp. 8913-8921 ◽  
Author(s):  
Nathalie Arbour ◽  
Robert Day ◽  
Jia Newcombe ◽  
Pierre J. Talbot
Keyword(s):  
Neurological Diseases ◽  
Point Mutations ◽  
Brain Parenchyma ◽  
N Gene ◽  
Respiratory Pathogens ◽  
Reverse Transcription Pcr ◽  
Human Coronaviruses ◽  
Human Brains

ABSTRACT Human coronaviruses (HCoV) cause common colds but can also infect neural cell cultures. To provide definitive experimental evidence for the neurotropism and neuroinvasion of HCoV and its possible association with multiple sclerosis (MS), we have performed an extensive search and characterization of HCoV RNA in a large panel of human brain autopsy samples. Very stringent reverse transcription-PCR with two primer pairs for both viral strains (229E and OC43), combined with Southern hybridization, was performed on samples from 90 coded donors with various neurological diseases (39 with MS and 26 with other neurological diseases) or normal controls (25 patients). We report that 44% (40 of 90) of donors were positive for 229E and that 23% (21 of 90) were positive for OC43. A statistically significant higher prevalence of OC43 in MS patients (35.9%; 14 of 39) than in controls (13.7%; 7 of 51) was observed. Sequencing of nucleocapsid protein (N) gene amplicons revealed point mutations in OC43, some consistently found in three MS patient brains and one normal control but never observed in laboratory viruses. In situ hybridization confirmed the presence of viral RNA in brain parenchyma, outside blood vessels. The presence of HCoV in human brains is consistent with neuroinvasion by these respiratory pathogens. Further studies are needed to distinguish between opportunistic and disease-associated viral presence in human brains.

scholarly journals Potential Differences in Cleavage of the S Protein and Type 1 Interferon Together Control Human Coronavirus Infection, Propagation, and Neuropathology within the Central Nervous System

2021 ◽  
Vol 95 (10) ◽  
Author(s):  
Alain Le Coupanec ◽  
Marc Desforges ◽  
Benedikt Kaufer ◽  
Philippe Dubeau ◽  
Marceline Côté ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Innate Immunity ◽  
Nervous System ◽  
Cns Infection ◽  
Respiratory Pathogens ◽  
S Protein ◽  
Type 1 Interferon ◽  
Viral Spread ◽  
Human Coronaviruses

ABSTRACT Human coronaviruses (HCoV) are respiratory pathogens which have been known since the 1960s. In December 2019, a new betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported, and it is responsible for one of the biggest pandemics of the last 2 centuries. Available evidence suggests that similar to the case with the HCoV-OC43 strain, SARS-CoV-2 neuroinvasion is associated with potential neurological disorders. Coronavirus infection of the central nervous system (CNS) is largely controlled by a viral factor, the spike glycoprotein (S), and a host factor, innate immunity. However, the interaction between these two factors remains elusive. Proteolytic cleavage of the S protein can occur at the interface between receptor binding (S1) and fusion (S2) domains (S1/S2), as well as in a position adjacent to a fusion peptide within S2 (S2′). In this study, using HCoV-OC43 as a surrogate for SARS-CoV-2, we determined that both S protein sites are involved in neurovirulence and are required for optimal CNS infection. Whereas efficient cleavage at S1/S2 is associated with decreased virulence, the potentially cleavable putative S2′ site is essential for efficient viral infection. Furthermore, type 1 interferon (IFN-1)-related innate immunity also plays an important role in the control of viral spread toward the spinal cord, by preventing infection of ependymal cells. Our results underline the link between the differential S cleavage and IFN-1 in the prevention of viral spread, to control the severity of infection and pathology in both immunocompetent and immunodeficient mice. Taken together, these results point toward two potential therapeutic antiviral targets: cleavage of the S protein in conjunction with efficient IFN-1-related innate immunity to prevent or at least reduce neuroinvasion, neural spread, and potential associated neurovirulence of human coronaviruses. IMPORTANCE Human coronaviruses (HCoV) are recognized respiratory pathogens. The emergence of the novel pathogenic member of this family in December 2019 (SARS-CoV-2, which causes COVID-19) poses a global health emergency. As with other coronaviruses reported previously, invasion of the human central nervous system (CNS), associated with diverse neurological disorders, was suggested for SARS-CoV-2. Herein, using the related HCoV-OC43 strain, we show that the viral spike protein constitutes a major neurovirulence factor and that type 1 interferon (IFN-1), in conjunction with cleavage of S protein by host proteases, represents an important host factor that participates in the control of CNS infection. To our knowledge, this is the first demonstration of a direct link between cleavage of the S protein, innate immunity, and neurovirulence. Understanding mechanisms of viral infection and spread in neuronal cells is essential to better design therapeutic strategies, and to prevent infection by human coronaviruses such as SARS-CoV-2 in the human CNS, especially in vulnerable populations such as the elderly and immunocompromised individuals.

scholarly journals Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43

2018 ◽  
Vol 92 (17) ◽  
Author(s):  
Mathieu Dubé ◽  
Alain Le Coupanec ◽  
Alan H. M. Wong ◽  
James M. Rini ◽  
Marc Desforges ◽  
...  
Keyword(s):  
Cell Culture ◽  
Brain Stem ◽  
Axonal Transport ◽  
Neurological Diseases ◽  
Neuronal Cell ◽  
Therapeutic Interventions ◽  
Respiratory Pathogens ◽  
Upper Respiratory Tract ◽  
Human Coronaviruses ◽  
The Brain

ABSTRACTHuman 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.IMPORTANCECoronaviruses 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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