scholarly journals Human Surfactant Protein D Binds Spike Protein and Acts as an Entry Inhibitor of SARS-CoV-2 Pseudotyped Viral Particles

2021 ◽  
Vol 12 ◽  
Author(s):  
Miao-Hsi Hsieh ◽  
Nazar Beirag ◽  
Valarmathy Murugaiah ◽  
Yu-Chi Chou ◽  
Wen-Shuo Kuo ◽  
...  
Keyword(s):  
Influenza A ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Protective Role ◽  
Spike Protein ◽  
Entry Inhibitor ◽  
Surfactant Protein D ◽  
Viral Inhibition ◽  
Immune Molecule

Human SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows its role in immune surveillance against pathogens. Higher levels of serum SP-D have been reported in the patients with severe acute respiratory syndrome coronavirus (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus in vitro, in vivo and ex vivo. In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing human angiotensin converting enzyme 2 (hACE2). The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following treatment with rfhSP-D (10 µg/ml). These results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merit pre-clinical studies in animal models.

scholarly journals Human Surfactant Protein D Binds S1 and Receptor Binding Domain of Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particles in vitro

2020 ◽  
Author(s):  
Miao-Hsi Hsieh ◽  
Nazar beirag ◽  
Valarmathy Murugaiah ◽  
Yu-Chi Chou ◽  
Wen-Shuo Kuo ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Protective Role ◽  
Binding Domain ◽  
Spike Protein ◽  
Entry Inhibitor ◽  
Surfactant Protein D ◽  
Receptor Binding Domain ◽  
Immune Molecule

AbstractHuman SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows immune surveillance role against pulmonary pathogens. Higher levels of serum SP-D have been reported in patients with severe acute respiratory syndrome coronavirus-1 (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus in vitro, in vivo and ex vivo models. In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing Angiotensin Converting Enzyme 2. The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following rfhSP-D treatment (10 μg/ml). The results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merits pre-clinical studies in murine models.

scholarly journals Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses.

1994 ◽  
Vol 94 (1) ◽  
pp. 311-319 ◽  
Author(s):  
K L Hartshorn ◽  
E C Crouch ◽  
M R White ◽  
P Eggleton ◽  
A I Tauber ◽  
...  
Keyword(s):  
Pulmonary Surfactant ◽  
Influenza A ◽  
Surfactant Protein ◽  
Protective Role ◽  
Surfactant Protein D ◽  
Influenza A Viruses ◽  
Pulmonary Surfactant Protein

scholarly journals NAction! How Can Neuraminidase-Based Immunity Contribute to Better Influenza Virus Vaccines?

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Florian Krammer ◽  
Ron A. M. Fouchier ◽  
Maryna C. Eichelberger ◽  
Richard J. Webby ◽  
Kathryn Shaw-Saliba ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Vaccine Development ◽  
Protective Role ◽  
National Institutes Of Health ◽  
Antigenic Drift ◽  
Centers Of Excellence ◽  
Open Questions ◽  
Infection Mechanisms

ABSTRACTNeuraminidase is one of the two surface glycoproteins of influenza A and B viruses. It has enzymatic activity that cleaves terminal sialic acid from glycans, and that activity is essential at several points in the virus life cycle. While neuraminidase is a major target for influenza antivirals, it is largely ignored in vaccine development. Current inactivated influenza virus vaccines might contain neuraminidase, but the antigen quantity and quality are varied and not standardized. While there are data that show a protective role of anti-neuraminidase immunity, many questions remain unanswered. These questions, among others, concern the targeted epitopes or antigenic sites, the potential for antigenic drift, and, connected to that, the breadth of protection, differences in induction of immune responses by vaccination versus infection, mechanisms of protection, the role of mucosal antineuraminidase antibodies, stability, and the immunogenicity of neuraminidase in vaccine formulations. Reagents for analysis of neuraminidase-based immunity are scarce, and assays are not widely used for clinical studies evaluating vaccines. However, efforts to better understand neuraminidase-based immunity have been made recently. A neuraminidase focus group, NAction!, was formed at a Centers of Excellence for Influenza Research and Surveillance meeting at the National Institutes of Health in Bethesda, MD, to promote research that helps to understand neuraminidase-based immunity and how it can contribute to the design of better and broadly protective influenza virus vaccines. Here, we review open questions and knowledge gaps that have been identified by this group and discuss how the gaps can be addressed, with the ultimate goal of designing better influenza virus vaccines.

scholarly journals Metabolic Determinants of Electrical Failure in Ex-Vivo Canine Model of Cardiac Arrest: Evidence for the Protective Role of Inorganic Pyrophosphate

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e57821 ◽  
Author(s):  
Junko Shibayama ◽  
Tyson G. Taylor ◽  
Paul W. Venable ◽  
Nathaniel L. Rhodes ◽  
Ryan B. Gil ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ex Vivo ◽  
Canine Model ◽  
Protective Role ◽  
Inorganic Pyrophosphate ◽  
Electrical Failure

scholarly journals The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury

2017 ◽  
Vol 312 (2) ◽  
pp. L155-L162 ◽  
Author(s):  
Hailin Zhao ◽  
Shiori Eguchi ◽  
Azeem Alam ◽  
Daqing Ma
Keyword(s):  
Lung Injury ◽  
Therapeutic Potential ◽  
Antioxidant Response ◽  
Protective Role ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Nuclear Factor ◽  
Obstructive Pulmonary Disease ◽  
Antioxidant Response Elements

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. Activation of Nrf2 has been shown to be protective against lung injury. In the lung, diverse stimuli including environmental oxidants, medicinal agents, and pathogens can activate Nrf2. Nrf2 translocates to the nucleus and binds to an ARE. Through transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary injury, abnormal inflammatory and immune responses, and apoptosis. The Nrf2-antioxidant pathway has been shown to be important in the protection against various lung injuries including acute lung injury/acute respiratory distress syndrome and bronchopulmonary dysplasia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and allergy and was widely examined for new therapeutic targets. The present review explores the protective role of Nrf-2 against lung injury and the therapeutic potential in targeting Nrf-2.

scholarly journals PTX3 Regulation of Inflammation, Hemostatic Response, Tissue Repair, and Resolution of Fibrosis Favors a Role in Limiting Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Andrea Doni ◽  
Alberto Mantovani ◽  
Barbara Bottazzi ◽  
Remo Castro Russo
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Life Quality ◽  
Unknown Origin ◽  
Protective Role

PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, rapidly produced at inflammatory sites by phagocytes and stromal cells in response to infection or tissue injury. PTX3 interacts with microbial moieties and selected pathogens, with molecules of the complement and hemostatic systems, and with extracellular matrix (ECM) components. In wound sites, PTX3 interacts with fibrin and plasminogen and favors a timely removal of fibrin-rich ECM for an efficient tissue repair. Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown origin, associated with excessive ECM deposition affecting tissue architecture, with irreversible loss of lung function and impact on the patient’s life quality. Maccarinelli et al. recently demonstrated a protective role of PTX3 using the bleomycin (BLM)-induced experimental model of lung fibrosis, in line with the reported role of PTX3 in tissue repair. However, the mechanisms and therapeutic potential of PTX3 in IPF remained to be investigated. Herein, we provide new insights on the possible role of PTX3 in the development of IPF and BLM-induced lung fibrosis. In mice, PTX3-deficiency was associated with worsening of the disease and with impaired fibrin removal and subsequently increased collagen deposition. In IPF patients, microarray data indicated a down-regulation of PTX3 expression, thus suggesting a potential rational underlying the development of disease. Therefore, we provide new insights for considering PTX3 as a possible target molecule underlying therapeutic intervention in IPF.

scholarly journals Protective Role of Lung Surfactant Protein D in a Murine Model of Invasive Pulmonary Aspergillosis

2001 ◽  
Vol 69 (4) ◽  
pp. 2728-2731 ◽  
Author(s):  
Taruna Madan ◽  
Uday Kishore ◽  
Mamta Singh ◽  
Peter Strong ◽  
Ejaj M. Hussain ◽  
...  
Keyword(s):  
Murine Model ◽  
Lung Surfactant ◽  
Invasive Pulmonary Aspergillosis ◽  
Surfactant Protein ◽  
Protective Role ◽  
Surfactant Protein D ◽  
Protective Effects ◽  
Pulmonary Aspergillosis ◽  
Lung Surfactant Protein

ABSTRACT The protective effects of intranasal administration of amphotericin B (AmB), human SP-A, SP-D and a 60-kDa fragment of SP-D (rSP-D) were examined in a murine model of invasive pulmonary aspergillosis (IPA). The untreated group of IPA mice showed no survival at 7 days postinfection. Treatment with AmB, SP-D, and rSP-D increased the survival rate to 80, 60, and 80%, respectively, suggesting that SP-D (and rSP-D) can protect immunosuppressed mice from an otherwise fatal challenge with Aspergillus fumigatus conidia.

scholarly journals Intestinally Secreted C-Type Lectin Reg3b Attenuates Salmonellosis but Not Listeriosis in Mice

2012 ◽  
Vol 80 (3) ◽  
pp. 1115-1120 ◽  
Author(s):  
Marleen T. J. van Ampting ◽  
Linda M. P. Loonen ◽  
Arjan J. Schonewille ◽  
Irene Konings ◽  
Carolien Vink ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Salmonella Enteritidis ◽  
Ex Vivo ◽  
Protective Role ◽  
Carbohydrate Binding ◽  
Intestinal Infection ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type

The Reg3 protein family, including the human member designated pancreatitis-associated protein (PAP), consists of secreted proteins that contain a C-type lectin domain involved in carbohydrate binding. They are expressed by intestinal epithelial cells. Colonization of germ-free mice and intestinal infection with pathogens increase the expression of Reg3g and Reg3b in the murine ileum. Reg3g is directly bactericidal for Gram-positive bacteria, but the exact role of Reg3b in bacterial infections is unknown. To investigate the possible protective role of Reg3b in intestinal infection, Reg3b knockout (Reg3b−/−) mice and wild-type (WT) mice were orally infected with Gram-negativeSalmonella enteritidisor Gram-positiveListeria monocytogenes. At day 2 after oralListeriainfection and at day 4 after oralSalmonellainfection, mice were sacrificed to collect intestinal and other tissues for pathogen quantification. Protein expression of Reg3b and Reg3g was determined in intestinal mucosal scrapings of infected and noninfected mice. In addition,ex vivobinding of ileal mucosal Reg3b toListeriaandSalmonellawas investigated. Whereas recovery ofSalmonellaorListeriafrom feces of Reg3b−/−mice did not differ from that from feces of WT mice, significantly higher numbers of viableSalmonella, but notListeria, bacteria were recovered from the colon, mesenteric lymph nodes, spleen, and liver of the Reg3b−/−mice than from those of WT mice. Mucosal Reg3b binds to both bacterial pathogens and may interfere with their mode of action. Reg3b plays a protective role against intestinal translocation of the Gram-negative bacteriumS. enteritidisin mice but not against the Gram-positive bacteriumL. monocytogenes.

scholarly journals Recent Advances on the Role and Therapeutic Potential of Regulatory T Cells in Atherosclerosis

2021 ◽  
Vol 10 (24) ◽  
pp. 5907
Author(s):  
Toru Tanaka ◽  
Naoto Sasaki ◽  
Yoshiyuki Rikitake
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Vascular Inflammation ◽  
Immunological Tolerance ◽  
Protective Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Recent Advances

Atherosclerotic diseases, including ischemic heart disease and stroke, are a main cause of mortality worldwide. Chronic vascular inflammation via immune dysregulation is critically involved in the pathogenesis of atherosclerosis. Accumulating evidence suggests that regulatory T cells (Tregs), responsible for maintaining immunological tolerance and suppressing excessive immune responses, play an important role in preventing the development and progression of atherosclerosis through the regulation of pathogenic immunoinflammatory responses. Several strategies to prevent and treat atherosclerosis through the promotion of regulatory immune responses have been developed, and could be clinically applied for the treatment of atherosclerotic cardiovascular disease. In this review, we summarize recent advances in our understanding of the protective role of Tregs in atherosclerosis and discuss attractive approaches to treat atherosclerotic disease by augmenting regulatory immune responses.

Sign in / Sign up

Export Citation Format

Share Document