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

Yifei Lang; Wentao Li; Zeshi Li; Danielle Koerhuis; Arthur C. S. van den Burg; Erik Rozemuller; Berend-Jan Bosch; Frank J. M. van Kuppeveld; Geert-Jan Boons; Eric G. Huizinga; Hilde M. van der Schaar; Raoul J. de Groot

doi:10.1073/pnas.2006299117

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2006299117 ◽

2020 ◽

Vol 117 (41) ◽

pp. 25759-25770 ◽

Cited By ~ 1

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.

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Coronavirus hemagglutinin-esterase and spike proteins co-evolve for functional balance and optimal virion avidity

10.1101/2020.04.03.003699 ◽

2020 ◽

Cited By ~ 1

Author(s):

Yifei Lang ◽

Wentao Li ◽

Zeshi Li ◽

Danielle Koerhuis ◽

Arthur C.S. van den Burg ◽

...

Keyword(s):

Influenza A ◽

Protein S ◽

Respiratory Pathogen ◽

Protein Species ◽

Influenza A Viruses ◽

Lectin Domain ◽

Functional Balance ◽

Worldwide Distribution ◽

Animal Pathogens ◽

Human Coronaviruses

ABSTRACTHuman coronaviruses OC43 and HKU1 are respiratory pathogen of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spill-over. 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 towards 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 selected for 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 co-evolve 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 (IAVs). Apparently, general principles fundamental to virion-sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens.

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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18189525 ◽

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.

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Evaluation of NxTAG Respiratory Pathogen Panel and Comparison with xTAG Respiratory Viral Panel Fast v2 and Film Array Respiratory Panel for Detecting Respiratory Pathogens in Nasopharyngeal Aspirates and Swine/Avian-Origin Influenza A Subtypes in Culture Isolates

Advances in Virology ◽

10.1155/2017/1324276 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

K. H. Chan ◽

K. K. W. To ◽

P. T. W. Li ◽

T. L. Wong ◽

R. Zhang ◽

...

Keyword(s):

Influenza A ◽

Clinical Laboratory ◽

Laboratory Diagnosis ◽

Influenza Viruses ◽

Respiratory Pathogen ◽

Respiratory Pathogens ◽

Rt Pcr ◽

Influenza A Viruses ◽

Avian Origin ◽

The Mean

This study evaluated a new multiplex kit, Luminex NxTAG Respiratory Pathogen Panel, for respiratory pathogens and compared it with xTAG RVP Fast v2 and FilmArray Respiratory Panel using nasopharyngeal aspirate specimens and culture isolates of different swine/avian-origin influenza A subtypes (H2N2, H5N1, H7N9, H5N6, and H9N2). NxTAG RPP gave sensitivity of 95.2%, specificity of 99.6%, PPV of 93.5%, and NPV of 99.7%. NxTAG RPP, xTAG RVP, and FilmArray RP had highly concordant performance among each other for the detection of respiratory pathogens. The mean analytic sensitivity (TCID50/ml) of NxTAG RPP, xTAG RVP, and FilmArray RP for detection of swine/avian-origin influenza A subtype isolates was 0.7, 41.8, and 0.8, respectively. All three multiplex assays correctly typed and genotyped the influenza viruses, except for NxTAG RRP that could not distinguish H3N2 from H3N2v. Further investigation should be performed if H3N2v is suspected to be the cause of disease. Sensitive and specific laboratory diagnosis of all influenza A viruses subtypes is especially essential in certain epidemic regions, such as Southeast Asia. The results of this study should help clinical laboratory professionals to be aware of the different performances of commercially available molecular multiplex RT-PCR assays that are commonly adopted in many clinical diagnostic laboratories.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1809667116 ◽

2019 ◽

Vol 116 (7) ◽

pp. 2681-2690 ◽

Cited By ~ 117

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.

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ATP catabolism by tissue nonspecific alkaline phosphatase contributes to development of ARDS in influenza-infected mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00149.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. L83-L92 ◽

Cited By ~ 3

Author(s):

Parker S. Woods ◽

Lauren M. Doolittle ◽

Judy M. Hickman-Davis ◽

Ian C. Davis

Keyword(s):

Alkaline Phosphatase ◽

Influenza A ◽

Influenza Infection ◽

High Capacity ◽

Receptor Activation ◽

Respiratory Pathogens ◽

Influenza A Viruses ◽

Epithelial Barrier Function ◽

Lung Dysfunction ◽

Tissue Nonspecific Alkaline Phosphatase

Influenza A viruses are highly contagious respiratory pathogens that are responsible for significant morbidity and mortality worldwide on an annual basis. We have shown previously that influenza infection of mice leads to increased ATP and adenosine accumulation in the airway lumen. Moreover, we demonstrated that A1-adenosine receptor activation contributes significantly to influenza-induced acute respiratory distress syndrome (ARDS). However, we found that development of ARDS in influenza-infected mice does not require catabolism of ATP to adenosine by ecto-5′-nucleotidase (CD73). Hence, we hypothesized that increased adenosine generation in response to infection is mediated by tissue nonspecific alkaline phosphatase (TNAP), which is a low-affinity, high-capacity enzyme that catabolizes nucleotides in a nonspecific manner. In the current study, we found that whole lung and BALF TNAP expression and alkaline phosphatase enzymatic activity increased as early as 2 days postinfection (dpi) of C57BL/6 mice with 10,000 pfu/mouse of influenza A/WSN/33 (H1N1). Treatment at 2 and 4 dpi with a highly specific quinolinyl-benzenesulfonamide TNAP inhibitor (TNAPi) significantly reduced whole lung alkaline phosphatase activity at 6 dpi but did not alter TNAP gene or protein expression. TNAPi treatment attenuated hypoxemia, lung dysfunction, histopathology, and pulmonary edema at 6 dpi without impacting viral replication or BALF adenosine. Treatment also improved epithelial barrier function and attenuated cellular and humoral immune responses to influenza infection. These data indicate that TNAP inhibition can attenuate influenza-induced ARDS by reducing inflammation and fluid accumulation within the lung. They also further emphasize the importance of adenosine generation for development of ARDS in influenza-infected mice.

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